Background: The antitumoral immune response is one determinant of colorectal cancer (CRC) outcome. Recent work suggests that Foxp3+CD25+CD4+ regulatory T cells (T4reg) might hamper effective immunosurveillance of emerging cancer cells and impede effective immune responses to established tumors. In this prospective study, we analyzed blood and tissue regulatory T cell populations in CRC patients.
Methods: Blood and tissue regulatory Foxp3+ T cells from 40 CRC patients were compared to regulatory Foxp3+ T cells from paired normal colonic tissue (NT) and from blood of healthy volunteers. Flow cytometry was used to quantify and phenotype all Foxp3+ T cell populations. Correlations were sought with the tumor stage and with micro-invasive status. The suppressive capacity of regulatory Foxp3+ T cells was assessed by their effect on CD4+CD25- T cell proliferation proliferation in vitro and by their capacity to inhibit cytokine production by conventional T cells.
Results: We found significant accumulation of CD8+CD25+Foxp3+ cells (T8reg) in blood and CRC tissue; their phenotype was close to that of T4reg. T8reg cells infiltrating CRC were activated, as suggested by increased CTLA-4, GITR and TGF-b1 expression compared to T8reg from paired normal tissue. Moreover, T8reg were able to suppress CD4+CD25- T cell proliferation and Th1 cytokine production ex vivo, demonstrating that tumor-infiltrating T8reg have strong suppressive capacities. T8reg numbers, but not T4reg numbers, correlated with the tumor stage and with micro-invasive status. Finally, IL-6 and TGF-b1 synergistically induced CD8+CD25+Foxp3+ T cell generation ex vivo.
Conclusions: We have identified a new regulatory T cell population (CD8+Foxp3+) with strong immunosuppressive properties in colorectal tumors. These cells may contribute to tumoral immune escape and disease progression.