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Inflammation Research

10.01.2018 | Review

Evolving notions on immune response in colorectal cancer and their implications for biomarker development

verfasst von: Fabio Grizzi, Gianluca Basso, Elena Monica Borroni, Tommaso Cavalleri, Paolo Bianchi, Sanja Stifter, Maurizio Chiriva-Internati, Alberto Malesci, Luigi Laghi

Erschienen in: Inflammation Research | Ausgabe 5/2018

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Abstract

Introduction

Colorectal cancer (CRC) still represents the third most commonly diagnosed type of cancer in men and women worldwide. CRC is acknowledged as a heterogeneous disease that develops through a multi-step sequence of events driven by clonal selections; this observation is sustained by the fact that histologically similar tumors may have completely different outcomes, including a varied response to therapy.

Methods

In “early” and “intermediate” stage of CRC (stages II and III, respectively) there is a compelling need for new biomarkers fit to assess the metastatic potential of their disease, selecting patients with aggressive disease that might benefit from adjuvant and targeted therapies. Therefore, we review the actual notions on immune response in colorectal cancer and their implications for biomarker development.

Results

The recognition of the key role of immune cells in human cancer progression has recently drawn attention on the tumor immune microenvironment, as a source of new indicators of tumor outcome and response to therapy. Thus, beside consolidated histopathological biomarkers, immune endpoints are now emerging as potential biomarkers.

Conclusions

The introduction of immune signatures and cellular and molecular components of the immune system as biomarkers is particularly important considering the increasing use of immune-based cancer therapies as therapeutic strategies for cancer patients.
Literatur
1.
Welch HG, Robertson DJ. Colorectal cancer on the decline—why screening can’t explain it all. N Engl J Med. 2016;374:1605–7.PubMedCrossRef
2.
Keane MG, Johnson GJ. Early diagnosis improves survival in colorectal cancer. Pract 2012;256:15–18.
3.
4.
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–E386.PubMedCrossRef
5.
Abdelsattar ZM, Wong SL, Regenbogen SE, Jomaa DM, Hardiman KM, Hendren S. Colorectal cancer outcomes and treatment patterns in patients too young for average-risk screening. Cancer. 2016;122:929–34.PubMedPubMedCentralCrossRef
6.
7.
Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990;61:759–67.PubMedCrossRef
8.
Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, et al. Genetic alterations during colorectal-tumor development. N Engl J Med. 1988;319:525–32.CrossRef
9.
Ilyas M, Tomlinson IP. Genetic pathways in colorectal cancer. Histopathology. 1996;28:389–99.CrossRef
10.
Walther A, Johnstone E, Swanton C, Midgley R, Tomlinson I, Kerr D. Genetic prognostic and predictive markers in colorectal cancer. Nat Rev Cancer. 2009;9:489–99.CrossRef
11.
Sugihara Y, Taniguchi H, Kushima R, Tsuda H, Kubota D, Ichikawa H, et al. Laser microdissection and two-dimensional difference gel electrophoresis reveal proteomic intra-tumor heterogeneity in colorectal cancer. J Proteom. 2013;78:134–47.CrossRef
12.
Vogelstein B, Kinzler KW. The multistep nature of cancer. TIG. 1993;9:138–41.CrossRef
13.
Al-Sohaily S, Biankin A, Leong R, Kohonen-Corish M, Warusavitarne J. Molecular pathways in colorectal cancer. J Gastroenterol Hepatol. 2012;27:1423–31.PubMedCrossRef
14.
Grizzi F, Celesti G, Basso G, Laghi L. Tumor budding as a potential histopathological biomarker in colorectal cancer: hype or hope? WJG. 2012;18:6532–6.PubMedPubMedCentralCrossRef
15.
George B, Kopetz S. Predictive and prognostic markers in colorectal cancer. Curr Oncol Rep. 2011;13:206–15.CrossRef
16.
Kelley RK, Venook AP. Prognostic and predictive markers in stage II colon cancer: is there a role for gene expression profiling? Clin Colorect Cancer. 2011;10:73–80.CrossRef
17.
18.
Malesci A, Laghi L, Bianchi P, Delconte G, Randolph A, Torri V, et al. Reduced likelihood of metastases in patients with microsatellite-unstable colorectal cancer. Clin Cancer Res. 2007;13:3831–9.PubMedCrossRef
19.
Sinicrope FA, Foster NR, Thibodeau SN, Marsoni S, Monges G, Labianca R, et al. DNA mismatch repair status and colon cancer recurrence and survival in clinical trials of 5-fluorouracil-based adjuvant therapy. J Natl Cancer Inst. 2011;103:863–75.CrossRef
20.
Andre T, de Gramont A, Vernerey D, Chibaudel B, Bonnetain F, Tijeras-Raballand A, et al. Adjuvant fluorouracil, leucovorin, and oxaliplatin in stage II to III colon cancer: updated 10-year survival and outcomes according to braf mutation and mismatch repair status of the MOSAIC study. J Clin Oncol. 2015;33:4176–87.PubMedCrossRef
21.
Laghi L, Bianchi P, Malesci A. Differences and evolution of the methods for the assessment of microsatellite instability. Oncogene. 2008;27:6313–21.PubMedCrossRef
22.
Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, et al. A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res. 1998;58:5248–57.PubMed
23.
Yashiro M, Laghi L, Saito K, Carethers JM, Slezak P, Rubio C, et al. Serrated adenomas have a pattern of genetic alterations that distinguishes them from other colorectal polyps. Cancer Epidemiol Biomark. 2005;14:2253–6.CrossRef
24.
Jass JR. Molecular heterogeneity of colorectal cancer: implications for cancer control. Surg Oncol. 2007;16(Suppl 1):S7–9.PubMedCrossRef
25.
Snover DC. Update on the serrated pathway to colorectal carcinoma. Hum Pathol. 2011;42:1–10.PubMedCrossRef
26.
Kriegl L, Vieth M, Kirchner T, Menssen A. Up-regulation of c-MYC and SIRT1 expression correlates with malignant transformation in the serrated route to colorectal cancer. Oncotarget. 2012;3:1182–93.PubMedPubMedCentralCrossRef
27.
Gaiser T, Meinhardt S, Hirsch D, Killian JK, Gaedcke J, Jo P, et al. Molecular patterns in the evolution of serrated lesion of the colorectum. Int J Cancer Journal international du cancer. 2013;132:1800–10.PubMedCrossRef
28.
Pino MS, Kikuchi H, Zeng M, Herraiz MT, Sperduti I, Berger D, et al. Epithelial to mesenchymal transition is impaired in colon cancer cells with microsatellite instability. Gastroenterology. 2010;138:1406–17.PubMedCrossRef
29.
Celesti G, Di Caro G, Bianchi P, Grizzi F, Basso G, Marchesi F, et al. Presence of Twist1-positive neoplastic cells in the stroma of chromosome-unstable colorectal tumors. Gastroenterology. 2013;145:647–57 (e15).CrossRef
30.
31.
Kronenberg M. Toward an understanding of NKT cell biology: progress and paradoxes. Annu Rev Immunol. 2005;23:877–900.PubMedCrossRef
32.
Kistner L, Doll D, Holtorf A, Nitsche U, Janssen KP. Interferon-inducible CXC-chemokines are crucial immune modulators and survival predictors in colorectal cancer. Oncotarget. 2017;8:89998–90012.PubMedPubMedCentralCrossRef
33.
Laghi L, Bianchi P, Miranda E, Balladore E, Pacetti V, Grizzi F, et al. CD3+ cells at the invasive margin of deeply invading (pT3–T4) colorectal cancer and risk of post-surgical metastasis: a longitudinal study. Lancet Oncol. 2009;10:877–84.CrossRef
34.
Malesci A, Bianchi P, Celesti G, Basso G, Marchesi F, Grizzi F, et al. Tumor-associated macrophages and response to 5-fluorouracil adjuvant therapy in stage III colorectal cancer. Oncoimmunology. 2017;6:e1342918.PubMedPubMedCentralCrossRef
35.
Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006;313:1960–4.PubMedCrossRef
36.
Galon J, Mlecnik B, Bindea G, Angell HK, Berger A, Lagorce C, et al. Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumours. J Pathol. 2014;232:199–209.PubMedCrossRef
37.
Galon J, Pages F, Marincola FM, Angell HK, Thurin M, Lugli A, et al. Cancer classification using the Immunoscore: a worldwide task force. J Transl Med. 2012;10:205.PubMedPubMedCentralCrossRef
38.
Mlecnik B, Bindea G, Angell HK, Maby P, Angelova M, Tougeron D, et al. Integrative analyses of colorectal cancer show immunoscore is a stronger predictor of patient survival than microsatellite instability. Immunity. 2016;44:698–711.PubMedCrossRef
39.
Gao P, Zhou X, Wang ZN, Song YX, Tong LL, Xu YY, et al. Which is a more accurate predictor in colorectal survival analysis? Nine data mining algorithms vs. the TNM staging system. PloS One. 2012;7:e42015.PubMedPubMedCentralCrossRef
40.
Malesci A, Laghi L. Novel prognostic biomarkers in colorectal cancer. Digest Dis. 2012;30:296–303.CrossRef
41.
Shia J, Klimstra DS, Bagci P, Basturk O, Adsay NV. TNM staging of colorectal carcinoma: issues and caveats. Semin Diagn Pathol. 2012;29:142–53.CrossRef
42.
Ueno H, Mochizuki H, Akagi Y, Kusumi T, Yamada K, Ikegami M, et al. Optimal colorectal cancer staging criteria in TNM classification. J Clin Oncol. 2012;30:1519–26.PubMedCrossRef
43.
Kim MJ, Jeong SY, Choi SJ, Ryoo SB, Park JW, Park KJ, et al. Survival paradox between stage IIB/C (T4N0) and stage IIIA (T1–2N1) colon cancer. Ann Surg Oncol. 2015;22:505–12.
44.
Puppa G, Sonzogni A, Colombari R, Pelosi G. TNM staging system of colorectal carcinoma: a critical appraisal of challenging issues. Arch Pathol Lab Med. 2010;134:837–52.
45.
Sinicrope FA, Shi Q. Combining molecular markers with the TNM staging system to improve prognostication in stage II and III colon cancer: are we ready yet? J Natl Cancer I. 2012;104:1616–8.CrossRef
46.
Deschoolmeester V, Baay M, Specenier P, Lardon F, Vermorken JB. A review of the most promising biomarkers in colorectal cancer: one step closer to targeted therapy. Oncol. 2010;15:699–731.
47.
Mandrekar SJ, Sargent DJ. Design of clinical trials for biomarker research in oncology. Clin Investig. 2011;1:1629–36.CrossRef
48.
Butterfield LH, Palucka AK, Britten CM, Dhodapkar MV, Hakansson L, Janetzki S, et al. Recommendations from the iSBTc-SITC/FDA/NCI workshop on immunotherapy biomarkers. Clin Cancer Res. 2011;17:3064–76.PubMedPubMedCentralCrossRef
49.
de Wit M, Fijneman RJ, Verheul HM, Meijer GA, Jimenez CR. Proteomics in colorectal cancer translational research: biomarker discovery for clinical applications. Clin Biochem. 2013;46:466–79.
50.
Mathivanan S, Ji H, Tauro BJ, Chen YS, Simpson RJ. Identifying mutated proteins secreted by colon cancer cell lines using mass spectrometry. J Proteom. 2012;76(Spec No.):141–9.CrossRef
51.
Peng Y, Li X, Wu M, Yang J, Liu M, Zhang W, et al. New prognosis biomarkers identified by dynamic proteomic analysis of colorectal cancer. Mol bioSyst. 2012;8:3077–88.PubMedCrossRef
52.
53.
Church D, Midgley R, Kerr D. Biomarkers in early-stage colorectal cancer: ready for prime time? Digest Dis. 2012;30(Suppl 2):27–33.CrossRef
54.
Legolvan MP, Taliano RJ, Resnick MB. Application of molecular techniques in the diagnosis, prognosis and management of patients with colorectal cancer: a practical approach. Hum Pathol. 2012;43:1157–68.PubMedCrossRef
55.
Sanz-Pamplona R, Berenguer A, Cordero D, Riccadonna S, Sole X, Crous-Bou M, et al. Clinical value of prognosis gene expression signatures in colorectal cancer: a systematic review. PloS One. 2012;7:e48877.PubMedPubMedCentralCrossRef
56.
Benson AB 3rd, Schrag D, Somerfield MR, Cohen AM, Figueredo AT, Flynn PJ, et al. American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol. 2004;22:3408–19.PubMedCrossRef
57.
Gill S, Loprinzi CL, Sargent DJ, Thome SD, Alberts SR, Haller DG, et al. Pooled analysis of fluorouracil-based adjuvant therapy for stage II and III colon cancer: who benefits and by how much? J Clin Oncol. 2004;22:1797–806.CrossRef
58.
McMillan DC, McArdle CS, Morrison DS. A clinical risk score to predict 3-, 5- and 10-year survival in patients undergoing surgery for Dukes B colorectal cancer. Br J Cancer. 2010;103:970–4.PubMedPubMedCentralCrossRef
59.
60.
Malesci A, Basso G, Bianchi P, Fini L, Grizzi F, Celesti G, et al. Molecular heterogeneity and prognostic implications of synchronous advanced colorectal neoplasia. Br J Cancer. 2014;110:1228–35.PubMedPubMedCentralCrossRef
61.
Nosho K, Kure S, Irahara N, Shima K, Baba Y, Spiegelman D, et al. A prospective cohort study shows unique epigenetic, genetic, and prognostic features of synchronous colorectal cancers. Gastroenterology. 2009;137:1609–20 e1-3.PubMedPubMedCentralCrossRef
62.
Cereda M, Gambardella G, Benedetti L, Iannelli F, Patel D, Basso G, et al. Patients with genetically heterogeneous synchronous colorectal cancer carry rare damaging germline mutations in immune-related genes. Nat Commun. 2016;7:12072.PubMedPubMedCentralCrossRef
63.
Cowin PA, Anglesio M, Etemadmoghadam D, Bowtell DD. Profiling the cancer genome. Annu Rev Genom Hum Genet. 2010;11:133–59.CrossRef
64.
Bustin SA, Murphy J. RNA biomarkers in colorectal cancer. Methods. 2013;59:116–25.CrossRef
65.
Deschoolmeester V, Boeckx C, Baay M, Weyler J, Wuyts W, Van Marck E, et al. KRAS mutation detection and prognostic potential in sporadic colorectal cancer using high-resolution melting analysis. Br J Cancer. 2010;103:1627–36.PubMedPubMedCentralCrossRef
66.
Ren JJ, Li GX, Ge J, Li X, Zhao YS. Is K-ras gene mutation a prognostic factor for colorectal cancer: a systematic review and meta-analysis. Dis Colon Rectum. 2012;55:913–23.PubMedCrossRef
67.
Ogino S, Shima K, Meyerhardt JA, McCleary NJ, Ng K, Hollis D, et al. Predictive and prognostic roles of BRAF mutation in stage III colon cancer: results from intergroup trial CALGB 89803. Clin Cancer Res. 2012;18:890–900.PubMedCrossRef
68.
Laghi L, Malesci A. Microsatellite instability and therapeutic consequences in colorectal cancer. Dig Dis. 2012;30:304–9.PubMedCrossRef
69.
Guastadisegni C, Colafranceschi M, Ottini L, Dogliotti E. Microsatellite instability as a marker of prognosis and response to therapy: a meta-analysis of colorectal cancer survival data. Eur J Cancer. 2010;46:2788–98.PubMedCrossRef
70.
Merok MA, Ahlquist T, Royrvik EC, Tufteland KF, Hektoen M, Sjo OH, et al. Microsatellite instability has a positive prognostic impact on stage II colorectal cancer after complete resection: results from a large, consecutive Norwegian series. Ann Oncol. 2013;24:1274–82.PubMedCrossRef
71.
Sinicrope FA, Sargent DJ. Molecular pathways: microsatellite instability in colorectal cancer: prognostic, predictive, and therapeutic implications. Clin Cancer Res. 2012;18:1506–12.PubMedPubMedCentralCrossRef
72.
Laghi L, Bianchi P, Roncalli M, Malesci A. Re. Revised Bethesda guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst. 2004;96:1402–3 (author reply 1403–4).PubMedCrossRef
73.
Popat S, Hubner R, Houlston RS. Systematic review of microsatellite instability and colorectal cancer prognosis. J Clin Oncol. 2005;23:609–18.PubMedCrossRef
74.
Giardiello FM, Allen JI, Axilbund JE, Boland CR, Burke CA, Burt RW, et al. Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US Multi-Society Task Force on colorectal cancer. Gastroenterology. 2014;147:502–26.CrossRef
75.
Stoffel EM, Mangu PB, Gruber SB, Hamilton SR, Kalady MF, Lau MWY, et al. Hereditary colorectal cancer syndromes: American society of clinical oncology clinical practice guideline endorsement of the familial risk–colorectal cancer: European Society for Medical Oncology Clinical Practice Guidelines. J Clin Oncol. 2015;33:209–17.PubMedCrossRef
76.
Valeri N, Gasparini P, Fabbri M, Braconi C, Veronese A, Lovat F, et al. Modulation of mismatch repair and genomic stability by miR-155. Proc Natl Acad Sci USA. 2010;107:6982–7.
77.
Valeri N, Gasparini P, Braconi C, Paone A, Lovat F, Fabbri M, et al. MicroRNA-21 induces resistance to 5-fluorouracil by down-regulating human DNA MutS homolog 2 (hMSH2). Proc Natl Acad Sci USA. 2010;107:21098–103.
78.
Moshayoff V, Faktor O, Laghi L, Celesti G, Peretz T, Keret D, et al. Feasibility of unbiased RNA profiling of colorectal tumors: a proof of principle. PloS One. 2016;11:e0159522.PubMedPubMedCentralCrossRef
79.
Siravegna G, Mussolin B, Buscarino M, Corti G, Cassingena A, Crisafulli G, et al. Clonal evolution and resistance to EGFR blockade in the blood of colorectal cancer patients. Nat Med. 2015;21:795–801.PubMedPubMedCentralCrossRef
80.
Bindea G, Mlecnik B, Fridman WH, Galon J. The prognostic impact of anti-cancer immune response: a novel classification of cancer patients. Semin Immunopathol. 2011;33:335–40.PubMedPubMedCentralCrossRef
81.
Zlobec I, Koelzer VH, Dawson H, Perren A, Lugli A. Next-generation tissue microarray (ngTMA) increases the quality of biomarker studies: an example using CD3, CD8, and CD45RO in the tumor microenvironment of six different solid tumor types. J Transl Med. 2013;11:104.PubMedPubMedCentralCrossRef
82.
83.
Coppola A, Arriga R, Lauro D, Del Principe MI, Buccisano F, Maurillo L, et al. NK cell inflammation in the clinical outcome of colorectal carcinoma. Front Med. 2015;2:33.CrossRef
84.
Shunyakov L, Ryan CK, Sahasrabudhe DM, Khorana AA. The influence of host response on colorectal cancer prognosis. Clin Colorect Cancer. 2004;4:38–45.CrossRef
85.
Titu LV, Monson JR, Greenman J. The role of CD8(+) T cells in immune responses to colorectal cancer. CII. 2002;51:235–47.
86.
Dalerba P, Maccalli C, Casati C, Castelli C, Parmiani G. Immunology and immunotherapy of colorectal cancer. Crit Rev Oncol Hemat. 2003;46:33–57.CrossRef
87.
Scurr M, Gallimore A, Godkin A. T cell subsets and colorectal cancer: discerning the good from the bad. Cell Immunol. 2012;279:21–4.PubMedCrossRef
88.
89.
90.
Zou W. Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol. 2006;6:295–307.PubMedCrossRef
91.
Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science. 2003;299:1057–61.PubMedCrossRef
92.
Fridman WH, Pages F, Sautes-Fridman C, Galon J. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer. 2012;12:298–306.PubMedCrossRef
93.
Alexander J, Watanabe T, Wu TT, Rashid A, Li S, Hamilton SR. Histopathological identification of colon cancer with microsatellite instability. Am J Pathol. 2001;158:527–35.CrossRef
94.
Graham DM, Appelman HD. Crohn’s-like lymphoid reaction and colorectal carcinoma: a potential histologic prognosticator. Modern Pathol. 1990;3:332–5.
95.
Aloisi F, Pujol-Borrell R. Lymphoid neogenesis in chronic inflammatory diseases. Nat Rev Immunol. 2006;6:205–17.PubMedCrossRef
96.
97.
Bergomas F, Grizzi F, Doni A, Pesce S, Laghi L, Allavena P, et al. Tertiary intratumor lymphoid tissue in colo-rectal cancer. Cancers. 2011;4:1–10.PubMedPubMedCentralCrossRef
98.
Mantovani A, Bottazzi B, Colotta F, Sozzani S, Ruco L. The origin and function of tumor-associated macrophages. Immunol Today. 1992;13:265–70.CrossRef
99.
100.
Mantovani A, Sica A. Macrophages, innate immunity and cancer: balance, tolerance, and diversity. Curr Opin Immunol. 2010;22:231–7.PubMedCrossRef
101.
Biswas SK, Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol. 2010;11:889–96.PubMedCrossRef
102.
Mantovani A, Romero P, Palucka AK, Marincola FM. Tumour immunity: effector response to tumour and role of the microenvironment. Lancet. 2008;371:771–83.CrossRef
103.
Joyce JA, Pollard JW. Microenvironmental regulation of metastasis. Nat Rev Cancer. 2009;9:239–52.PubMedCrossRef
104.
Murdoch C, Muthana M, Coffelt SB, Lewis CE. The role of myeloid cells in the promotion of tumour angiogenesis. Nat Rev Cancer. 2008;8:618–31.PubMedCrossRef
105.
Allavena P, Sica A, Garlanda C, Mantovani A. The Yin-Yang of tumor-associated macrophages in neoplastic progression and immune surveillance. Immunol Rev. 2008;222:155–61.PubMedCrossRef
106.
Biswas SK, Gangi L, Paul S, Schioppa T, Saccani A, Sironi M, et al. A distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF-kappa B and enhanced IRF-3/STAT1 activation). Blood. 2006;107:2112–22.PubMedCrossRef
107.
Solinas G, Schiarea S, Liguori M, Fabbri M, Pesce S, Zammataro L, et al. Tumor-conditioned macrophages secrete migration-stimulating factor: a new marker for M2-polarization, influencing tumor cell motility. J Immunol. 2010;185:642–52.PubMedCrossRef
108.
Mantovani A, Peri G, Polentarutti N, Bolis G, Mangioni C, Spreafico F. Effects on in vitro tumor growth of macrophages isolated from human ascitic ovarian tumors. Int J Cancer Journal international du cancer. 1979;23:157–64.
109.
Mantovani A, Allavena P, Sessa C, Bolis G, Mangioni C. Natural killer activity of lymphoid cells isolated from human ascitic ovarian tumors. Int J Cancer Journal international du cancer. 1980;25:573–82.
110.
Forssell J, Oberg A, Henriksson ML, Stenling R, Jung A, Palmqvist R. High macrophage infiltration along the tumor front correlates with improved survival in colon cancer. Clin Cancer Res. 2007;13:1472–9.PubMedCrossRef
111.
Beatty GL, Chiorean EG, Fishman MP, Saboury B, Teitelbaum UR, Sun WJ, et al. CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science. 2011;331:1612–6.PubMedPubMedCentralCrossRef
112.
Parcesepe P, Giordano G, Laudanna C, Febbraro A, Pancione M. Cancer-associated immune resistance and evasion of immune surveillance in colorectal cancer. Gastroenterol Res Pract. 2016;2016:6261721.PubMedPubMedCentralCrossRef
113.
Gulubova M, Manolova I, Kyurkchiev D, Julianov A, Altunkova I. Decrease in intrahepatic CD56 + lymphocytes in gastric and colorectal cancer patients with liver metastases. APMIS. 2009;117:870–9.PubMedCrossRef
114.
Marechal R, De Schutter J, Nagy N, Demetter P, Lemmers A, Deviere J, et al. Putative contribution of CD56 positive cells in cetuximab treatment efficacy in first-line metastatic colorectal cancer patients. BMC Cancer. 2010;10:340.PubMedPubMedCentralCrossRef
115.
Menon AG, Janssen-van Rhijn CM, Morreau H, Putter H, Tollenaar RA, van de Velde CJ, et al. Immune system and prognosis in colorectal cancer: a detailed immunohistochemical analysis. Lab Investig J Tech Methods Pathol. 2004;84:493–501.CrossRef
116.
Sandel MH, Speetjens FM, Menon AG, Albertsson PA, Basse PH, Hokland M, et al. Natural killer cells infiltrating colorectal cancer and MHC class I expression. Mol Immunol. 2005;42:541–6.PubMedCrossRef
117.
Halama N, Braun M, Kahlert C, Spille A, Quack C, Rahbari N, et al. Natural killer cells are scarce in colorectal carcinoma tissue despite high levels of chemokines and cytokines. Clin Cancer Res. 2011;17:678–89.CrossRef
118.
Coca S, Perez-Piqueras J, Martinez D, Colmenarejo A, Saez MA, Vallejo C, et al. The prognostic significance of intratumoral natural killer cells in patients with colorectal carcinoma. Cancer. 1997;79:2320–8.PubMedCrossRef
119.
Sconocchia G, Eppenberger S, Spagnoli GC, Tornillo L, Droeser R, Caratelli S, et al. NK cells and T cells cooperate during the clinical course of colorectal cancer. Oncoimmunology. 2014;3:e952197.PubMedPubMedCentralCrossRef
120.
Furue H, Matsuo K, Kumimoto H, Hiraki A, Suzuki T, Yatabe Y, et al. Decreased risk of colorectal cancer with the high natural killer cell activity NKG2D genotype in Japanese. Carcinogenesis. 2008;29:316–20.CrossRef
121.
Gharagozloo M, Kalantari H, Rezaei A, Maracy MR, Salehi M, Bahador A, et al. The decrease in NKG2D + Natural Killer cells in peripheral blood of patients with metastatic colorectal cancer. Bratislavske lekarske listy. 2015;116:296–301.PubMed
122.
Rocca YS, Roberti MP, Arriaga JM, Amat M, Bruno L, Pampena MB, et al. Altered phenotype in peripheral blood and tumor-associated NK cells from colorectal cancer patients. Innate Immun. 2013;19:76–85.PubMedCrossRef
123.
Bindea G, Mlecnik B, Tosolini M, Kirilovsky A, Waldner M, Obenauf AC, et al. Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer. Immunity. 2013;39:782–95.CrossRef
124.
Fridman WH, Galon J, Pages F, Tartour E, Sautes-Fridman C, Kroemer G. Prognostic and predictive impact of intra- and peritumoral immune infiltrates. Cancer Res. 2011;71:5601–5.PubMedCrossRef
125.
Pages F, Berger A, Camus M, Sanchez-Cabo F, Costes A, Molidor R, et al. Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med. 2005;353:2654–66.PubMedCrossRef
126.
Pages F, Galon J, Dieu-Nosjean MC, Tartour E, Sautes-Fridman C, Fridman WH. Immune infiltration in human tumors: a prognostic factor that should not be ignored. Oncogene. 2010;29:1093–102.CrossRef
127.
Salama P, Phillips M, Grieu F, Morris M, Zeps N, Joseph D, et al. Tumor-infiltrating FOXP3(+) T regulatory cells show strong prognostic significance in colorectal cancer. J Clin Oncol. 2009;27:186–192.PubMedCrossRef
128.
Nosho K, Baba Y, Tanaka N, Shima K, Hayashi M, Meyerhardt JA, et al. Tumour-infiltrating T-cell subsets, molecular changes in colorectal cancer, and prognosis: cohort study and literature review. J Pathol. 2010;222:350–66.CrossRef
129.
130.
Koch M, Beckhove P, Op den Winkel J, Autenrieth D, Wagner P, Nummer D, et al. Tumor infiltrating T lymphocytes in colorectal cancer: tumor-selective activation and cytotoxic activity in situ. Ann Surg. 2006;244:986–92 (discussion 992–3).CrossRef
131.
Atreya I, Schimanski CC, Becker C, Wirtz S, Dornhoff H, Schnurer E, et al. The T-box transcription factor eomesodermin controls CD8 T cell activity and lymph node metastasis in human colorectal cancer. Gut. 2007;56:1572–8.PubMedPubMedCentralCrossRef
132.
Pollard JW. Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer. 2004;4:71–8.PubMedCrossRef
133.
Bingle L, Brown NJ, Lewis CE. The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies. J Pathol. 2002;196:254–65.CrossRef
134.
Edin S, Wikberg ML, Dahlin AM, Rutegard J, Oberg A, Oldenborg PA, et al. The distribution of macrophages with a M1 or M2 phenotype in relation to prognosis and the molecular characteristics of colorectal cancer. PloS One. 2012;7:e47045.PubMedPubMedCentralCrossRef
135.
Zhou Q, Peng RQ, Wu XJ, Xia Q, Hou JH, Ding Y, et al. The density of macrophages in the invasive front is inversely correlated to liver metastasis in colon cancer. J Transl Med. 2010;8:13.PubMedPubMedCentralCrossRef
136.
Kang JC, Chen JS, Lee CH, Chang JJ, Shieh YS. Intratumoral macrophage counts correlate with tumor progression in colorectal cancer. J Surg Oncol. 2010;102:242–8.PubMedCrossRef
137.
Ohnishi K, Komohara Y, Saito Y, Miyamoto Y, Watanabe M, Baba H, et al. CD169-positive macrophages in regional lymph nodes are associated with a favorable prognosis in patients with colorectal carcinoma. Cancer Sci. 2013;104:1237–44.PubMedCrossRef
138.
Farinha P, Masoudi H, Skinnider BF, Shumansky K, Spinelli JJ, Gill K, et al. Analysis of multiple biomarkers shows that lymphoma-associated macrophage (LAM) content is an independent predictor of survival in follicular lymphoma (FL). Blood. 2005;106:2169–74.PubMedCrossRef
139.
Alvaro T, Lejeune M, Camacho FI, Salvado MT, Sanchez L, Garcia JF, et al. The presence of STAT1-positive tumor-associated macrophages and their relation to outcome in patients with follicular lymphoma. Haematologica. 2006;91:1605–12.PubMed
140.
Taskinen M, Karjalainen-Lindsberg ML, Nyman H, Eerola LM, Leppa S. A high tumor-associated macrophage content predicts favorable outcome in follicular lymphoma patients treated with rituximab and cyclophosphamide-doxorubicin-vincristine-prednisone. Clin Cancer Res. 2007;13:5784–9.PubMedCrossRef
141.
Kridel R, Xerri L, Gelas-Dore B, Tan K, Feugier P, Vawda A, et al. The prognostic impact of CD163-positive macrophages in follicular lymphoma: a study from the BC cancer agency and the lymphoma study association. Clin Cancer Res. 2015;21:3428–35.PubMedCrossRef
142.
143.
Kirchberger S, Royston DJ, Boulard O, Thornton E, Franchini F, Szabady RL, et al. Innate lymphoid cells sustain colon cancer through production of interleukin-22 in a mouse model. J Exp Med. 2013;210:917–31.CrossRef
144.
Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12:252–64.CrossRef
145.
146.
Singh PP, Sharma PK, Krishnan G, Lockhart AC. Immune checkpoints and immunotherapy for colorectal cancer. Gastroenterol Rep. 2015;3:289–97.CrossRef
147.
Llosa NJ, Cruise M, Tam A, Wicks EC, Hechenbleikner EM, Taube JM, et al. The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints. Cancer Discov. 2015;5:43–51.PubMedCrossRef
148.
Bilgin B, Sendur MA, Bulent Akinci M, Sener Dede D, Yalcin B. Targeting the PD-1 pathway: a new hope for gastrointestinal cancers. Curr Med Res Opin. 2017;33:749–59.PubMedCrossRef
149.
Passardi A, Canale M, Valgiusti M, Ulivi P. Immune checkpoints as a target for colorectal cancer treatment. Int J Mol Sci. 2017;18:1324.PubMedCentralCrossRef
150.
151.
Basso G, Bianchi P, Malesci A, Laghi L. Hereditary or sporadic polyposis syndromes. Best Pract Res Clin Gastroenterol. 2017;31:409–17.PubMedCrossRef
152.
Dudley JC, Lin MT, Le DT, Eshleman JR. Microsatellite instability as a biomarker for PD-1 blockade. Clin Cancer Res. 2016;22:813–20.CrossRef
153.
Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372:2509–20.PubMedPubMedCentralCrossRef
154.
Overman MJ, McDermott R, Leach JL, Lonardi S, Lenz HJ, Morse MA, et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol. 2017;18:1182–91.PubMedCrossRef
155.
Khosravi Shahi P, Fernandez Pineda I. Tumoral angiogenesis: review of the literature. Cancer Investig. 2008;26:104–8.CrossRef
156.
Achen MG, Stacker SA. Molecular control of lymphatic metastasis. Ann N Y Acad Sci. 2008;1131:225–34.CrossRef
157.
Bonecchi R, Galliera E, Borroni EM, Corsi MM, Locati M, Mantovani A. Chemokines and chemokine receptors: an overview. Front Biosci. 2009;14:540–51.
158.
Zlotnik A, Yoshie O. Chemokines: a new classification system and their role in immunity. Immunity. 2000;12:121–7.PubMedCrossRef
159.
Murphy PM. The molecular biology of leukocyte chemoattractant receptors. Annu Rev Immunol. 1994;12:593–633.PubMedCrossRef
160.
Scotton C, Milliken D, Wilson J, Raju S, Balkwill F. Analysis of CC chemokine and chemokine receptor expression in solid ovarian tumours. Br J Cancer. 2001;85:891–7.PubMedPubMedCentralCrossRef
161.
Conti I, Rollins BJ. CCL2 (monocyte chemoattractant protein-1) and cancer. Semin Cancer Biol. 2004;14:149–54.CrossRef
162.
163.
Kulbe H, Levinson NR, Balkwill F, Wilson JL. The chemokine network in cancer—much more than directing cell movement. Int J Dev Biol. 2004;48:489–96.PubMedCrossRef
164.
Trujillo G, O’Connor EC, Kunkel SL, Hogaboam CM. A novel mechanism for CCR4 in the regulation of macrophage activation in bleomycin-induced pulmonary fibrosis. Am J Pathol 2008;172:1209–21.PubMedPubMedCentralCrossRef
165.
Mantovani A, Bussolino F, Introna M. Cytokine regulation of endothelial cell function: from molecular level to the bedside. Immunol Today. 1997;18:231–40.CrossRef
166.
Sickert D, Aust DE, Langer S, Haupt I, Baretton GB, Dieter P. Characterization of macrophage subpopulations in colon cancer using tissue microarrays. Histopathology. 2005;46:515–21.CrossRef
167.
Muller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, et al. Involvement of chemokine receptors in breast cancer metastasis. Nature. 2001;410:50–6.CrossRef
168.
Kawada K, Hosogi H, Sonoshita M, Sakashita H, Manabe T, Shimahara Y, et al. Chemokine receptor CXCR3 promotes colon cancer metastasis to lymph nodes. Oncogene. 2007;26:4679–88.PubMedCrossRef
169.
Lin K, Zou R, Lin F, Zheng S, Shen X, Xue X. Expression and effect of CXCL14 in colorectal carcinoma. Mol Med Rep. 2014;10:1561–8.PubMedCrossRef
170.
Akeus P, Langenes V, von Mentzer A, Yrlid U, Sjoling A, Saksena P, et al. Altered chemokine production and accumulation of regulatory T cells in intestinal adenomas of APC(Min/+) mice. Cancer Immunol Immun. 2014;63:807–19.CrossRef
171.
Dimberg J, Skarstedt M, Lofgren S, Zar N, Matussek A. Protein expression and gene polymorphism of CXCL10 in patients with colorectal cancer. Biomed Rep. 2014;2:340–3.PubMedPubMedCentralCrossRef
172.
Lu J, Zhao J, Feng H, Wang P, Zhang Z, Zong Y, et al. Antitumor efficacy of CC motif chemokine ligand 19 in colorectal cancer. Digest Dis Sci. 2014;59:2153–62.PubMedCrossRef
173.
Cheng XS, Li YF, Tan J, Sun B, Xiao YC, Fang XB, et al. CCL20 and CXCL8 synergize to promote progression and poor survival outcome in patients with colorectal cancer by collaborative induction of the epithelial-mesenchymal transition. Cancer Lett. 2014;348:77–87.PubMedCrossRef
174.
Yamada S, Shimada M, Utsunomiya T, Morine Y, Imura S, Ikemoto T, et al. CXC receptor 4 and stromal cell-derived factor 1 in primary tumors and liver metastases of colorectal cancer. J Surg Res. 2014;187:107–12.
175.
Heckmann D, Maier P, Laufs S, Li L, Sleeman JP, Trunk MJ, et al. The disparate twins: a comparative study of CXCR4 and CXCR7 in SDF-1alpha-induced gene expression, invasion and chemosensitivity of colon cancer. Clin Cancer Res. 2014;20:604–16.CrossRef
176.
D’Alterio C, Avallone A, Tatangelo F, Delrio P, Pecori B, Cella L, et al. A prognostic model comprising pT stage, N status, and the chemokine receptors CXCR4 and CXCR7 powerfully predicts outcome in neoadjuvant resistant rectal cancer patients. Int J Cancer Journal international du cancer. 2014;135:379–90.
177.
Cao B, Yang Y, Pan Y, Jia Y, Brock MV, Herman JG, et al. Epigenetic silencing of CXCL14 induced colorectal cancer migration and invasion. Discovery medicine. 2013;16:137–47.
178.
Zeng J, Yang XD, Cheng L, Liu R, Lei YL, Dong DD, et al. Chemokine CXCL14 is associated with prognosis in patients with colorectal carcinoma after curative resection. J Transl Med. 2013;11:6.PubMedPubMedCentralCrossRef
179.
Tada N, Tsuno NH, Kawai K, Murono K, Nirei T, Ishihara S, et al. Changes in the plasma levels of cytokines/chemokines for predicting the response to chemoradiation therapy in rectal cancer patients. Oncol Rep. 2014;31:463–71.CrossRef
180.
Malara A, Currao M, Gruppi C, Celesti G, Viarengo G, Buracchi C, et al. Megakaryocytes contribute to the bone marrow-matrix environment by expressing fibronectin, type IV collagen, and laminin. Stem Cells. 2014;32:926–37.CrossRef
181.
West NR, McCuaig S, Franchini F, Powrie F. Emerging cytokine networks in colorectal cancer. Nat Rev Immunol. 2015;15:615–29.CrossRef
182.
Olsen RS, Nijm J, Andersson RE, Dimberg J, Wagsater D. Circulating inflammatory factors associated with worse long-term prognosis in colorectal cancer. WJG. 2017;23:6212–9.PubMedPubMedCentralCrossRef
183.
Chang PH, Pan YP, Fan CW, Tseng WK, Huang JS, Wu TH, et al. Pretreatment serum interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha levels predict the progression of colorectal cancer. Cancer Med. 2016;5:426–33.CrossRef
184.
185.
Wu J, Wang Y, Xu X, Cao H, Sahengbieke S, Sheng H, et al. Transcriptional activation of FN1 and IL11 by HMGA2 promotes the malignant behavior of colorectal cancer. Carcinogenesis. 2016;37:511–21.
186.
187.
Housseau F, Wu S, Wick EC, Fan H, Wu X, Llosa NJ, et al. Redundant innate and adaptive sources of IL17 production drive colon tumorigenesis. Cancer Res. 2016;76:2115–24.PubMedPubMedCentralCrossRef
188.
Rochman Y, Spolski R, Leonard WJ. New insights into the regulation of T cells by gamma(c) family cytokines. Nat Rev Immunol. 2009;9:480–90.CrossRef
Metadaten
Titel
Evolving notions on immune response in colorectal cancer and their implications for biomarker development
verfasst von
Fabio Grizzi
Gianluca Basso
Elena Monica Borroni
Tommaso Cavalleri
Paolo Bianchi
Sanja Stifter
Maurizio Chiriva-Internati
Alberto Malesci
Luigi Laghi
Publikationsdatum
10.01.2018
Verlag
Springer International Publishing
Erschienen in
Inflammation Research / Ausgabe 5/2018
Print ISSN: 1023-3830
Elektronische ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-017-1128-1

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