Skip to main content
Erschienen in: Digestive Diseases and Sciences 2/2021

19.03.2020 | Original Article

Comparison of Immune Microenvironment Between Colon and Liver Metastatic Tissue in Colon Cancer Patients with Liver Metastasis

verfasst von: Su-Na Zhou, Wen-Tao Pan, Meng-Xian Pan, Qiu-Yun Luo, Lin Zhang, Jun-Zhong Lin, Yu-Jie Zhao, Xiang-Lei Yan, Lu-Ping Yuan, Yu-Xin Zhang, Da-Jun Yang, Miao-Zhen Qiu

Erschienen in: Digestive Diseases and Sciences | Ausgabe 2/2021

Einloggen, um Zugang zu erhalten

Abstract

Background

Liver metastasis is an indicator of unfavorable responses to immunotherapy in colorectal cancer patients. However, the difference of immune microenvironment between primary tumors and liver metastases has not been well understood.

Patients and Methods

Fifty-four colon cancer with liver metastasis patients who received resection of both primary and metastasis lesions have been analyzed. The immune score is based on the density of infiltrating immune cells (CD3+ cell, CD8+ cell, CD11b+ cell, CD11c+ cell, and CD33+ cell) in the center and margin of the tumor. The expression of immune markers between the primary tumor and hepatic metastases was analyzed using Wilcoxon’s signed rank test.

Results

All the five markers had higher expression in tumor margins than center tumor in both primary tumor and hepatic metastases lesions. The expression of CD11c and CD11b had no difference between metastatic lesions and primary tumor. In tumor margins, except CD11b, all the other 4 markers expressed significantly higher in hepatic metastases than in primary tumor. Intra-tumor, CD3 had higher expression in primary tumor than in hepatic metastases, while CD33 had higher expression in hepatic metastases than in primary tumor. CD8+ CD3+ cells of the total CD8+ cell population in primary tumor was significantly higher than in hepatic metastases (36.42% vs. 24.88%, p = 0.0069).

Conclusions

The immune microenvironment between primary tumor and hepatic metastasis is different. More immunosuppressing cells in liver may partially explain why immunotherapy in colon cancer is less effective with liver metastatic disease.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Darvin P, Toor SM, Sasidharan Nair V, Elkord E. Immune checkpoint inhibitors: recent progress and potential biomarkers. Exp Mol Med. 2018;50:165.CrossRef Darvin P, Toor SM, Sasidharan Nair V, Elkord E. Immune checkpoint inhibitors: recent progress and potential biomarkers. Exp Mol Med. 2018;50:165.CrossRef
2.
Zurück zum Zitat Ahn BC, Pyo KH, Xin CF, et al. Comprehensive analysis of the characteristics and treatment outcomes of patients with non-small cell lung cancer treated with anti-PD-1 therapy in real-world practice. J Cancer Res Clin Oncol. 2019;145:1613–1623.CrossRef Ahn BC, Pyo KH, Xin CF, et al. Comprehensive analysis of the characteristics and treatment outcomes of patients with non-small cell lung cancer treated with anti-PD-1 therapy in real-world practice. J Cancer Res Clin Oncol. 2019;145:1613–1623.CrossRef
3.
Zurück zum Zitat Garde-Noguera J, Martin-Martorell P, De Julian M, et al. Predictive and prognostic clinical and pathological factors of nivolumab efficacy in non-small-cell lung cancer patients. Clin Transl Oncol. 2018;20:1072–1079.CrossRef Garde-Noguera J, Martin-Martorell P, De Julian M, et al. Predictive and prognostic clinical and pathological factors of nivolumab efficacy in non-small-cell lung cancer patients. Clin Transl Oncol. 2018;20:1072–1079.CrossRef
4.
Zurück zum Zitat Nosrati A, Tsai KK, Goldinger SM, et al. Evaluation of clinicopathological factors in PD-1 response: derivation and validation of a prediction scale for response to PD-1 monotherapy. Br J Cancer. 2017;116:1141–1147.CrossRef Nosrati A, Tsai KK, Goldinger SM, et al. Evaluation of clinicopathological factors in PD-1 response: derivation and validation of a prediction scale for response to PD-1 monotherapy. Br J Cancer. 2017;116:1141–1147.CrossRef
5.
Zurück zum Zitat Tamiya M, Tamiya A, Inoue T, et al. Metastatic site as a predictor of nivolumab efficacy in patients with advanced non-small cell lung cancer: a retrospective multicenter trial. PLoS ONE. 2018;13:e0192227.CrossRef Tamiya M, Tamiya A, Inoue T, et al. Metastatic site as a predictor of nivolumab efficacy in patients with advanced non-small cell lung cancer: a retrospective multicenter trial. PLoS ONE. 2018;13:e0192227.CrossRef
6.
Zurück zum Zitat Tumeh PC, Hellmann MD, Hamid O, et al. Liver metastasis and treatment outcome with anti-PD-1 monoclonal antibody in patients with melanoma and NSCLC. Cancer Immunol Res. 2017;5:417–424.CrossRef Tumeh PC, Hellmann MD, Hamid O, et al. Liver metastasis and treatment outcome with anti-PD-1 monoclonal antibody in patients with melanoma and NSCLC. Cancer Immunol Res. 2017;5:417–424.CrossRef
7.
Zurück zum Zitat Gordon SR, Maute RL, Dulken BW, et al. PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity. Nature. 2017;545:495–499.CrossRef Gordon SR, Maute RL, Dulken BW, et al. PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity. Nature. 2017;545:495–499.CrossRef
8.
Zurück zum Zitat Mayo SC, Pawlik TM. Current management of colorectal hepatic metastasis. Expert Rev Gastroenterol Hepatol. 2009;3:131.CrossRef Mayo SC, Pawlik TM. Current management of colorectal hepatic metastasis. Expert Rev Gastroenterol Hepatol. 2009;3:131.CrossRef
9.
Zurück zum Zitat Vibert E, Canedo L, Adam R. Strategies to treat primary unresectable colorectal liver metastases. Semin Oncol. 2005;32:33–39.CrossRef Vibert E, Canedo L, Adam R. Strategies to treat primary unresectable colorectal liver metastases. Semin Oncol. 2005;32:33–39.CrossRef
10.
Zurück zum Zitat Kemeny N. Management of liver metastases from colorectal cancer. Oncology. 2006;20:1161–1176.PubMed Kemeny N. Management of liver metastases from colorectal cancer. Oncology. 2006;20:1161–1176.PubMed
11.
Zurück zum Zitat Lau WY, Lai ECH. Hepatic resection for colorectal liver metastases. Singap Med J. 2007;48:635–639. Lau WY, Lai ECH. Hepatic resection for colorectal liver metastases. Singap Med J. 2007;48:635–639.
12.
Zurück zum Zitat Xu J, Fan J, Qin X, et al. Chinese guidelines for the diagnosis and comprehensive treatment of colorectal liver metastases (version 2018). J Cancer Res Clin Oncol. 2019;145:725–736.CrossRef Xu J, Fan J, Qin X, et al. Chinese guidelines for the diagnosis and comprehensive treatment of colorectal liver metastases (version 2018). J Cancer Res Clin Oncol. 2019;145:725–736.CrossRef
13.
Zurück zum Zitat Simoneau E, Vauthey JN. Progression of colorectal cancer liver metastasis after chemotherapy: a new test of time? Ann Surg Oncol. 2018;25:1469–1470.CrossRef Simoneau E, Vauthey JN. Progression of colorectal cancer liver metastasis after chemotherapy: a new test of time? Ann Surg Oncol. 2018;25:1469–1470.CrossRef
14.
Zurück zum Zitat Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372:2509–2520.CrossRef Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372:2509–2520.CrossRef
15.
Zurück zum Zitat Angelova M, Mlecnik B, Vasaturo A, et al. Evolution of metastases in space and time under immune selection. Cell. 2018;175:751–765.e16.CrossRef Angelova M, Mlecnik B, Vasaturo A, et al. Evolution of metastases in space and time under immune selection. Cell. 2018;175:751–765.e16.CrossRef
16.
Zurück zum Zitat Becht E, Giraldo NA, Germain C, et al. Immune contexture, immunoscore, and malignant cell molecular subgroups for prognostic and theranostic classifications of cancers. Adv Immunol. 2016;130:95–190.CrossRef Becht E, Giraldo NA, Germain C, et al. Immune contexture, immunoscore, and malignant cell molecular subgroups for prognostic and theranostic classifications of cancers. Adv Immunol. 2016;130:95–190.CrossRef
17.
Zurück zum Zitat McLemore LE, Janakiram M, Albanese J, et al. An immunoscore using PD-L1, CD68, and tumor-infiltrating lymphocytes (TILs) to predict response to neoadjuvant chemotherapy in invasive breast cancer. Appl Immunohistochem Mol Morphol. 2018;26:611–619.CrossRef McLemore LE, Janakiram M, Albanese J, et al. An immunoscore using PD-L1, CD68, and tumor-infiltrating lymphocytes (TILs) to predict response to neoadjuvant chemotherapy in invasive breast cancer. Appl Immunohistochem Mol Morphol. 2018;26:611–619.CrossRef
18.
Zurück zum Zitat Zou MX, Lv GH, Wang XB, et al. Clinical impact of the immune microenvironment in spinal chordoma: immunoscore as an independent favorable prognostic factor. Neurosurgery. 2019;84:E318–E333.CrossRef Zou MX, Lv GH, Wang XB, et al. Clinical impact of the immune microenvironment in spinal chordoma: immunoscore as an independent favorable prognostic factor. Neurosurgery. 2019;84:E318–E333.CrossRef
19.
Zurück zum Zitat Sherwood AM, Emerson RO, Scherer D, et al. Tumor-infiltrating lymphocytes in colorectal tumors display a diversity of T cell receptor sequences that differ from the T cells in adjacent mucosal tissue. Cancer Immunol Immunother. 2013;62:1453–1461.CrossRef Sherwood AM, Emerson RO, Scherer D, et al. Tumor-infiltrating lymphocytes in colorectal tumors display a diversity of T cell receptor sequences that differ from the T cells in adjacent mucosal tissue. Cancer Immunol Immunother. 2013;62:1453–1461.CrossRef
20.
Zurück zum Zitat Kmiecik J, Poli A, Brons NH, et al. Elevated CD3+ and CD8+ tumor-infiltrating immune cells correlate with prolonged survival in glioblastoma patients despite integrated immunosuppressive mechanisms in the tumor microenvironment and at the systemic level. J Neuroimmunol. 2013;264:71–83.CrossRef Kmiecik J, Poli A, Brons NH, et al. Elevated CD3+ and CD8+ tumor-infiltrating immune cells correlate with prolonged survival in glioblastoma patients despite integrated immunosuppressive mechanisms in the tumor microenvironment and at the systemic level. J Neuroimmunol. 2013;264:71–83.CrossRef
21.
Zurück zum Zitat Wang Y, Lin HC, Huang MY, et al. The immunoscore system predicts prognosis after liver metastasectomy in colorectal cancer liver metastases. Cancer Immunol Immunother. 2018;67:435–444.CrossRef Wang Y, Lin HC, Huang MY, et al. The immunoscore system predicts prognosis after liver metastasectomy in colorectal cancer liver metastases. Cancer Immunol Immunother. 2018;67:435–444.CrossRef
22.
Zurück zum Zitat Zhang QQ, Hu XW, Liu YL, et al. CD11b deficiency suppresses intestinal tumor growth by reducing myeloid cell recruitment. Sci Rep. 2015;5:15948.CrossRef Zhang QQ, Hu XW, Liu YL, et al. CD11b deficiency suppresses intestinal tumor growth by reducing myeloid cell recruitment. Sci Rep. 2015;5:15948.CrossRef
23.
Zurück zum Zitat Schmid MC, Khan SQ, Kaneda MM, et al. Integrin CD11b activation drives anti-tumor innate immunity. Nat Commun. 2018;9:5379.CrossRef Schmid MC, Khan SQ, Kaneda MM, et al. Integrin CD11b activation drives anti-tumor innate immunity. Nat Commun. 2018;9:5379.CrossRef
24.
Zurück zum Zitat Sun HL, Zhou X, Xue YF, et al. Increased frequency and clinical significance of myeloid-derived suppressor cells in human colorectal carcinoma. World J Gastroenterol. 2012;18:3303–3309.PubMedPubMedCentral Sun HL, Zhou X, Xue YF, et al. Increased frequency and clinical significance of myeloid-derived suppressor cells in human colorectal carcinoma. World J Gastroenterol. 2012;18:3303–3309.PubMedPubMedCentral
25.
Zurück zum Zitat Yang R, Cai TT, Wu XJ, et al. Tumour YAP1 and PTEN expression correlates with tumour-associated myeloid suppressor cell expansion and reduced survival in colorectal cancer. Immunology. 2018;155:263–272.CrossRef Yang R, Cai TT, Wu XJ, et al. Tumour YAP1 and PTEN expression correlates with tumour-associated myeloid suppressor cell expansion and reduced survival in colorectal cancer. Immunology. 2018;155:263–272.CrossRef
26.
Zurück zum Zitat Rostamzadeh D, Haghshenas MR, Daryanoosh F, et al. Altered frequency of CD8(+) CD11c(+) T cells and expression of immunosuppressive molecules in lymphoid organs of mouse model of colorectal cancer. J Cell Physiol. 2019;234:11986–11998.CrossRef Rostamzadeh D, Haghshenas MR, Daryanoosh F, et al. Altered frequency of CD8(+) CD11c(+) T cells and expression of immunosuppressive molecules in lymphoid organs of mouse model of colorectal cancer. J Cell Physiol. 2019;234:11986–11998.CrossRef
27.
Zurück zum Zitat Wang Y, Lin HC, Huang MY, et al. The immunoscore system predicts prognosis after liver metastasectomy in colorectal cancer liver metastases. Cancer Immunol Immunother. 2017;67:1–10. Wang Y, Lin HC, Huang MY, et al. The immunoscore system predicts prognosis after liver metastasectomy in colorectal cancer liver metastases. Cancer Immunol Immunother. 2017;67:1–10.
28.
Zurück zum Zitat Patel S, Chung SH, White G, Bao S, Celermajer DS. The “atheroprotective” mediators apolipoprotein A-I and Foxp3 are over-abundant in unstable carotid plaques. Int J Cardiol. 2010;145:183–187.CrossRef Patel S, Chung SH, White G, Bao S, Celermajer DS. The “atheroprotective” mediators apolipoprotein A-I and Foxp3 are over-abundant in unstable carotid plaques. Int J Cardiol. 2010;145:183–187.CrossRef
29.
Zurück zum Zitat Jamal R, Lapointe R, Cocolakis E, et al. Peripheral and local predictive immune signatures identified in a phase II trial of ipilimumab with carboplatin/paclitaxel in unresectable stage III or stage IV melanoma. J Immunother Cancer. 2017;5:83.CrossRef Jamal R, Lapointe R, Cocolakis E, et al. Peripheral and local predictive immune signatures identified in a phase II trial of ipilimumab with carboplatin/paclitaxel in unresectable stage III or stage IV melanoma. J Immunother Cancer. 2017;5:83.CrossRef
30.
Zurück zum Zitat Markl B, Wieberneit J, Kretsinger H, et al. Number of intratumoral T lymphocytes is associated with lymph node size, lymph node harvest, and outcome in node-negative colon cancer. Am J Clin Pathol. 2016;145:826–836.CrossRef Markl B, Wieberneit J, Kretsinger H, et al. Number of intratumoral T lymphocytes is associated with lymph node size, lymph node harvest, and outcome in node-negative colon cancer. Am J Clin Pathol. 2016;145:826–836.CrossRef
31.
Zurück zum Zitat Pages F, Mlecnik B, Marliot F, et al. International validation of the consensus Immunoscore for the classification of colon cancer: a prognostic and accuracy study. Lancet. 2018;391:2128–2139.CrossRef Pages F, Mlecnik B, Marliot F, et al. International validation of the consensus Immunoscore for the classification of colon cancer: a prognostic and accuracy study. Lancet. 2018;391:2128–2139.CrossRef
32.
Zurück zum Zitat Richards CH, Roxburgh CS, Powell AG, Foulis AK, Horgan PG, McMillan DC. The clinical utility of the local inflammatory response in colorectal cancer. Eur J Cancer. 2014;50:309–319.CrossRef Richards CH, Roxburgh CS, Powell AG, Foulis AK, Horgan PG, McMillan DC. The clinical utility of the local inflammatory response in colorectal cancer. Eur J Cancer. 2014;50:309–319.CrossRef
33.
Zurück zum Zitat Toor SM, Syed Khaja AS, El Salhat H, et al. Increased levels of circulating and tumor-infiltrating granulocytic myeloid cells in colorectal cancer patients. Front Immunol. 2016;7:560.CrossRef Toor SM, Syed Khaja AS, El Salhat H, et al. Increased levels of circulating and tumor-infiltrating granulocytic myeloid cells in colorectal cancer patients. Front Immunol. 2016;7:560.CrossRef
34.
Zurück zum Zitat Sottoriva A, Spiteri I, Piccirillo SG, et al. Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics. Proc Natl Acad Sci USA. 2013;110:4009–4014.CrossRef Sottoriva A, Spiteri I, Piccirillo SG, et al. Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics. Proc Natl Acad Sci USA. 2013;110:4009–4014.CrossRef
35.
Zurück zum Zitat Thorn M, Point GR, Burga RA, Nguyen CT, Joseph Espat N, Katz SC. Liver metastases induce reversible hepatic B cell dysfunction mediated by Gr-1+ CD11b+ myeloid cells. J Leukoc Biol. 2014;96:883–894.CrossRef Thorn M, Point GR, Burga RA, Nguyen CT, Joseph Espat N, Katz SC. Liver metastases induce reversible hepatic B cell dysfunction mediated by Gr-1+ CD11b+ myeloid cells. J Leukoc Biol. 2014;96:883–894.CrossRef
36.
Zurück zum Zitat Halama N, Zoernig I, Berthel A, et al. Tumoral immune cell exploitation in colorectal cancer metastases can be targeted effectively by anti-CCR5 therapy in cancer patients. Cancer Cell. 2016;29:587–601.CrossRef Halama N, Zoernig I, Berthel A, et al. Tumoral immune cell exploitation in colorectal cancer metastases can be targeted effectively by anti-CCR5 therapy in cancer patients. Cancer Cell. 2016;29:587–601.CrossRef
37.
Zurück zum Zitat Forestier C, Park SH, Wei D, Benlagha K, Teyton L, Bendelac A. T cell development in mice expressing CD1d directed by a classical MHC class II promoter. J Immunol. 2003;171:4096–4104.CrossRef Forestier C, Park SH, Wei D, Benlagha K, Teyton L, Bendelac A. T cell development in mice expressing CD1d directed by a classical MHC class II promoter. J Immunol. 2003;171:4096–4104.CrossRef
38.
Zurück zum Zitat Schimanski CC, Moehler M, Gockel I, et al. Expression of chemokine receptor CCR5 correlates with the presence of hepatic molecular metastases in K-ras positive human colorectal cancer. J Cancer Res Clin Oncol. 2011;137:1139–1145.CrossRef Schimanski CC, Moehler M, Gockel I, et al. Expression of chemokine receptor CCR5 correlates with the presence of hepatic molecular metastases in K-ras positive human colorectal cancer. J Cancer Res Clin Oncol. 2011;137:1139–1145.CrossRef
39.
Zurück zum Zitat Qian DC, Xiao X, Byun J, et al. PI3K/Akt/mTOR signaling and plasma membrane proteins are implicated in responsiveness to adjuvant dendritic cell vaccination for metastatic colorectal cancer. Clin Cancer Res. 2017;23:399–406.CrossRef Qian DC, Xiao X, Byun J, et al. PI3K/Akt/mTOR signaling and plasma membrane proteins are implicated in responsiveness to adjuvant dendritic cell vaccination for metastatic colorectal cancer. Clin Cancer Res. 2017;23:399–406.CrossRef
Metadaten
Titel
Comparison of Immune Microenvironment Between Colon and Liver Metastatic Tissue in Colon Cancer Patients with Liver Metastasis
verfasst von
Su-Na Zhou
Wen-Tao Pan
Meng-Xian Pan
Qiu-Yun Luo
Lin Zhang
Jun-Zhong Lin
Yu-Jie Zhao
Xiang-Lei Yan
Lu-Ping Yuan
Yu-Xin Zhang
Da-Jun Yang
Miao-Zhen Qiu
Publikationsdatum
19.03.2020
Verlag
Springer US
Erschienen in
Digestive Diseases and Sciences / Ausgabe 2/2021
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-020-06203-8

Weitere Artikel der Ausgabe 2/2021

Digestive Diseases and Sciences 2/2021 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

29.05.2024 Larynxkarzinom Nachrichten

Fast ein Viertel der Personen mit mäßig dysplastischen Stimmlippenläsionen entwickelt einen Kehlkopftumor. Solche Personen benötigen daher eine besonders enge ärztliche Überwachung.

Nach Herzinfarkt mit Typ-1-Diabetes schlechtere Karten als mit Typ 2?

29.05.2024 Herzinfarkt Nachrichten

Bei Menschen mit Typ-2-Diabetes sind die Chancen, einen Myokardinfarkt zu überleben, in den letzten 15 Jahren deutlich gestiegen – nicht jedoch bei Betroffenen mit Typ 1.

15% bedauern gewählte Blasenkrebs-Therapie

29.05.2024 Urothelkarzinom Nachrichten

Ob Patienten und Patientinnen mit neu diagnostiziertem Blasenkrebs ein Jahr später Bedauern über die Therapieentscheidung empfinden, wird einer Studie aus England zufolge von der Radikalität und dem Erfolg des Eingriffs beeinflusst.

Costims – das nächste heiße Ding in der Krebstherapie?

28.05.2024 Onkologische Immuntherapie Nachrichten

„Kalte“ Tumoren werden heiß – CD28-kostimulatorische Antikörper sollen dies ermöglichen. Am besten könnten diese in Kombination mit BiTEs und Checkpointhemmern wirken. Erste klinische Studien laufen bereits.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.