gms | German Medical Science

27. Deutscher Krebskongress

Deutsche Krebsgesellschaft e. V.

22. - 26.03.2006, Berlin

PD-1/PD-L1 expression in colorectal cancer and its implications for apoptosis and tumor immune evasion

Meeting Abstract

  • corresponding author presenting/speaker Martin Gasser - Universitätsklinikum, Würzburg, Deutschland
  • Martin Grimm - Universitätsklinikum, Würzburg
  • Ekatherina Nichiporuk - Universitätsklinikum, Würzburg
  • Marco Bueter - Universitätsklinikum, Würzburg
  • Tatiana Lebedeva - American Red Cross, HLA Laboratory, Boston, USA
  • Jens Lutz - Universitätsklinikum, Klinikum rechts der Isar, München
  • Matthias Koenigshausen - Universitätsklinikum, Würzburg
  • Andreas Thalheimer - Universitätsklinikum, Würzburg
  • Arnulf Thiede - Universitätsklinikum, Würzburg
  • Uwe Heemann - Universitätsklinikum, Klinikum rechts der Isar, München
  • Detlef Meyer - Universitätsklinikum, Würzburg
  • Ana Maria Waaga-Gasser - Universitätsklinikum, Würzburg

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocPO207

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter:

Veröffentlicht: 20. März 2006

© 2006 Gasser et al.
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There is evidence that the PD-1 (programmed death 1)/ PD-L1 signaling pathway is an important mechanism for tumors to evade T cell recognition in particular by an up-regulation of PD-L1 in tumors. Here we compared the expression of PD-1/PD-L1 together with (anti-) apoptotic genes, cytokines, and T cell subpopulations in tumor tissues of patients with primary colorectal cancer at different stages. Eighty one patients who underwent surgery for primary colorectal cancer were included in this study and assigned to groups according to their UICC stage. Expression of PD-1/PD-L1, (anti-) apoptotic genes, cytokines, and T cell subpopulations in tumor tissues were assessed using double immunostaining, immunofluorescence and Real Time PCR. In contrast to the expression of PD-1 with a low expression at advanced stages and a high expression at early stages, PD-L1 expression on tumor cells was significantly increased in tumor tissues of patients with stage III/IV tumors. We then assessed the interaction between tumor and effector cells. Double positive staining for the expression of PD-1/PD-L1 was observed in tissues of patients in early tumor stages. Co-localization of CD4+ cells with PD-1 was predominantly detectable in UICC III/IV patients whereas PD-L1 expression on CD4+ cells was particularly found at early stages. To analyze whether regulatory T cells may be involved in the process of evasion from the immune surveillance, CD4+CD25+CTLA4+ as well as CD4/Foxp3 were used. Strong expression of CD4+CD25+CTLA4+ as well as an increased expression of CD4+Foxp3 was observed in tumors of stage III/IV patients compared to early stages. In addition, a significant increase of IL-10 as well as a decrease of IFN-γ expression were observed in tumors of stage III/IV patients. TGF-β/TGF-βR expression increased at higher tumor stages. High expression of TGF-ß receptor II in tumors correlated with a progressive course of the disease and tumor relapses, i.e. TGF-ß RII in early tumor stages was indicative for early tumor progress. These data indicate that regulatory T cells are involved in the process of evasion and PD-L1 plays a key role during tumor progression. The observation that PD-1/PD-L1 expression was increased at early tumor stages suggests that this interaction could mediate inhibitory signals (via tumor cells expressing PD-L1) to effector T cells enabling the tumor to progress. PD-L1 blockade may prove to be a valuable approach for cancer immunotherapy.