Skip to main content
Erschienen in: Cancer Immunology, Immunotherapy 7/2013

01.07.2013 | Review

Immune-suppressive properties of the tumor microenvironment

verfasst von: Jürgen C. Becker, Mads Hald Andersen, David Schrama, Per thor Straten

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 7/2013

Einloggen, um Zugang zu erhalten

Abstract

Solid tumors are more than an accumulation of cancer cells. Indeed, cancerous cells create a permissive microenvironment by exploiting non-transformed host cells. Thus, solid tumors rather resemble abnormal organs composed of the cancerous cells itself and the stroma providing the supportive framework. The stroma can be divided into the extracellular matrix consisting of proteoglycans, hyaluronic acid, and fibrous proteins, as well as stromal cells including mesenchymal and immune cells; moreover, it contains various peptide factors and metabolites. Here, we will focus on immune-modulating capacities of the tumor microenvironment.
Literatur
12.
Zurück zum Zitat Brennan PJ, Brigl M, Brenner MB (2013) Invariant natural killer T cells: an innate activation scheme linked to diverse effector functions. Nat Rev Immunol 13:101–117. doi:10.1038/nri3369 PubMedCrossRef Brennan PJ, Brigl M, Brenner MB (2013) Invariant natural killer T cells: an innate activation scheme linked to diverse effector functions. Nat Rev Immunol 13:101–117. doi:10.​1038/​nri3369 PubMedCrossRef
16.
Zurück zum Zitat Yu Q, Stamenkovic I (2000) Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis. Gen Dev 14:163–176 Yu Q, Stamenkovic I (2000) Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis. Gen Dev 14:163–176
17.
Zurück zum Zitat Sheu BC, Hsu SM, Ho HN et al (2001) A novel role of metalloproteinase in cancer-mediated immunosuppression. Cancer Res 61:237–242PubMed Sheu BC, Hsu SM, Ho HN et al (2001) A novel role of metalloproteinase in cancer-mediated immunosuppression. Cancer Res 61:237–242PubMed
18.
Zurück zum Zitat Boutet P, Agüera-González S, Atkinson S et al (2009) Cutting edge: the metalloproteinase ADAM17/TNF-alpha-converting enzyme regulates proteolytic shedding of the MHC class I-related chain B protein. J Immunol 182:49–53PubMed Boutet P, Agüera-González S, Atkinson S et al (2009) Cutting edge: the metalloproteinase ADAM17/TNF-alpha-converting enzyme regulates proteolytic shedding of the MHC class I-related chain B protein. J Immunol 182:49–53PubMed
24.
33.
Zurück zum Zitat Jayaraman P, Parikh F, Lopez-Rivera E et al (2012) Tumor-expressed inducible nitric oxide synthase controls induction of functional myeloid-derived suppressor cells through modulation of vascular endothelial growth factor release. J Immunol 188:5365–5376. doi:10.4049/jimmunol.1103553 PubMedCrossRef Jayaraman P, Parikh F, Lopez-Rivera E et al (2012) Tumor-expressed inducible nitric oxide synthase controls induction of functional myeloid-derived suppressor cells through modulation of vascular endothelial growth factor release. J Immunol 188:5365–5376. doi:10.​4049/​jimmunol.​1103553 PubMedCrossRef
36.
Zurück zum Zitat Shime H, Yabu M, Akazawa T et al (2008) Tumor-secreted lactic acid promotes IL-23/IL-17 proinflammatory pathway. J Immunol 180:7175–7183PubMed Shime H, Yabu M, Akazawa T et al (2008) Tumor-secreted lactic acid promotes IL-23/IL-17 proinflammatory pathway. J Immunol 180:7175–7183PubMed
37.
Zurück zum Zitat Cham CM, Gajewski TF (2005) Glucose availability regulates IFN-gamma production and p70S6 kinase activation in CD8+ effector T cells. J Immunol 174:4670–4677PubMed Cham CM, Gajewski TF (2005) Glucose availability regulates IFN-gamma production and p70S6 kinase activation in CD8+ effector T cells. J Immunol 174:4670–4677PubMed
38.
Zurück zum Zitat Mandapathil M, Szczepanski MJ, Szajnik M et al (2010) Adenosine and prostaglandin E2 cooperate in the suppression of immune responses mediated by adaptive regulatory T cells. J Biol Chem 285:27571–27580. doi:10.1074/jbc.M110.127100 PubMedCrossRef Mandapathil M, Szczepanski MJ, Szajnik M et al (2010) Adenosine and prostaglandin E2 cooperate in the suppression of immune responses mediated by adaptive regulatory T cells. J Biol Chem 285:27571–27580. doi:10.​1074/​jbc.​M110.​127100 PubMedCrossRef
40.
Zurück zum Zitat Haskó G, Linden J, Cronstein B, Pacher P (2008) Adenosine receptors: therapeutic aspects for inflammatory and immune diseases. Nat Rev Drug Discov 7:759–770. doi:10.1038/nrd2638 PubMedCrossRef Haskó G, Linden J, Cronstein B, Pacher P (2008) Adenosine receptors: therapeutic aspects for inflammatory and immune diseases. Nat Rev Drug Discov 7:759–770. doi:10.​1038/​nrd2638 PubMedCrossRef
42.
Zurück zum Zitat Su Y, Jackson EK, Gorelik E (2011) Receptor desensitization and blockade of the suppressive effects of prostaglandin E(2) and adenosine on the cytotoxic activity of human melanoma-infiltrating T lymphocytes. Cancer Immunol Immunother 60:111–122. doi:10.1007/s00262-010-0924-z PubMedCrossRef Su Y, Jackson EK, Gorelik E (2011) Receptor desensitization and blockade of the suppressive effects of prostaglandin E(2) and adenosine on the cytotoxic activity of human melanoma-infiltrating T lymphocytes. Cancer Immunol Immunother 60:111–122. doi:10.​1007/​s00262-010-0924-z PubMedCrossRef
43.
Zurück zum Zitat Häusler SFM, Montalbán del Barrio I, Strohschein J et al (2011) Ectonucleotidases CD39 and CD73 on OvCA cells are potent adenosine-generating enzymes responsible for adenosine receptor 2A-dependent suppression of T cell function and NK cell cytotoxicity. Cancer Immunol Immunother 60:1405–1418. doi:10.1007/s00262-011-1040-4 PubMedCrossRef Häusler SFM, Montalbán del Barrio I, Strohschein J et al (2011) Ectonucleotidases CD39 and CD73 on OvCA cells are potent adenosine-generating enzymes responsible for adenosine receptor 2A-dependent suppression of T cell function and NK cell cytotoxicity. Cancer Immunol Immunother 60:1405–1418. doi:10.​1007/​s00262-011-1040-4 PubMedCrossRef
52.
Zurück zum Zitat Reck M, Bondarenko I, Luft A et al (2013) Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy in extensive-disease-small-cell lung cancer: results from a randomized, double-blind, multicenter phase 2 trial. Ann Oncol 24:75–83. doi:10.1093/annonc/mds213 PubMedCrossRef Reck M, Bondarenko I, Luft A et al (2013) Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy in extensive-disease-small-cell lung cancer: results from a randomized, double-blind, multicenter phase 2 trial. Ann Oncol 24:75–83. doi:10.​1093/​annonc/​mds213 PubMedCrossRef
55.
Zurück zum Zitat Santegoets SJAM, Stam AGM, Lougheed SM et al (2012) T cell profiling reveals high CD4(+)CTLA-4 (+) T cell frequency as dominant predictor for survival after prostate GVAX/ipilimumab treatment. Cancer Immunol Immunother. doi:10.1007/s00262-012-1330-5 PubMed Santegoets SJAM, Stam AGM, Lougheed SM et al (2012) T cell profiling reveals high CD4(+)CTLA-4 (+) T cell frequency as dominant predictor for survival after prostate GVAX/ipilimumab treatment. Cancer Immunol Immunother. doi:10.​1007/​s00262-012-1330-5 PubMed
58.
Zurück zum Zitat Liakou CI, Kamat A, Tang DN et al (2008) CTLA-4 blockade increases IFNgamma-producing CD4+ ICOShi cells to shift the ratio of effector to regulatory T cells in cancer patients. Proc Nat Acad Sci 105:14987–14992. doi:10.1073/pnas.0806075105 PubMedCrossRef Liakou CI, Kamat A, Tang DN et al (2008) CTLA-4 blockade increases IFNgamma-producing CD4+ ICOShi cells to shift the ratio of effector to regulatory T cells in cancer patients. Proc Nat Acad Sci 105:14987–14992. doi:10.​1073/​pnas.​0806075105 PubMedCrossRef
60.
Zurück zum Zitat Hamid O, Schmidt H, Nissan A et al (2011) A prospective phase II trial exploring the association between tumor microenvironment biomarkers and clinical activity of ipilimumab in advanced melanoma. J Transl Med 9:204. doi:10.1186/1479-5876-9-204 PubMedCrossRef Hamid O, Schmidt H, Nissan A et al (2011) A prospective phase II trial exploring the association between tumor microenvironment biomarkers and clinical activity of ipilimumab in advanced melanoma. J Transl Med 9:204. doi:10.​1186/​1479-5876-9-204 PubMedCrossRef
61.
65.
Zurück zum Zitat Hobo W, Novobrantseva TI, Fredrix H et al (2012) Improving dendritic cell vaccine immunogenicity by silencing PD-1 ligands using siRNA-lipid nanoparticles combined with antigen mRNA electroporation. Cancer Immunol Immunother. doi:10.1007/s00262-012-1334-1 PubMed Hobo W, Novobrantseva TI, Fredrix H et al (2012) Improving dendritic cell vaccine immunogenicity by silencing PD-1 ligands using siRNA-lipid nanoparticles combined with antigen mRNA electroporation. Cancer Immunol Immunother. doi:10.​1007/​s00262-012-1334-1 PubMed
75.
76.
78.
Zurück zum Zitat Taylor DD, Doellgast GJ (1979) Quantitation of peroxidase-antibody binding to membrane fragments using column chromatography. Anal Biochem 98:53–59PubMedCrossRef Taylor DD, Doellgast GJ (1979) Quantitation of peroxidase-antibody binding to membrane fragments using column chromatography. Anal Biochem 98:53–59PubMedCrossRef
Metadaten
Titel
Immune-suppressive properties of the tumor microenvironment
verfasst von
Jürgen C. Becker
Mads Hald Andersen
David Schrama
Per thor Straten
Publikationsdatum
01.07.2013
Verlag
Springer-Verlag
Erschienen in
Cancer Immunology, Immunotherapy / Ausgabe 7/2013
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-013-1434-6

Weitere Artikel der Ausgabe 7/2013

Cancer Immunology, Immunotherapy 7/2013 Zur Ausgabe

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

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