Critical role for CD8+FoxP3+ regulatory T cells in colon cancer immune response in humans
- 1Department of Oncology and Transplantation, and Immunology-Gastroenterology Unit, University of Paris 12 and Henri Mondor Hospital AP-HP, Créteil, France
- 2Department of Biological Immunology. University of Paris 12, Henri Mondor Hospital AP-HP, Créteil, France
- Professor Iradj Sobhani, Service d’HepatoGastroEnterology, 51 Av Mal deLattre de Tassigny, Créteil 94010, France;
Colorectal cancer (CRC) immunosurveillance is based on innate and adaptive immune effector cells, and various cytokines and chemokines are involved in the identification and destruction of cancer cells. Survival of patients depends on the density and function of these cells. Very recent studies highlighted the particular role of tumour cells themselves in initiating the antitumoural immune response.
WHY SHOULD WE TAKE FOXP3-POSITIVE REGULATORY T CELLS INTO CONSIDERATION?
Pronounced lymphocytic infiltration of colon or rectal tumour tissues is linked with longer patient survival, and immune suppression enhances the chance of appearance of cancer in human and animal models. The phenotypes of these cells (ie, CD8+ T cells (central and effector memory CD8+ T cells) and CD4+ T cells (CD4+ T helper cells of types 1, 2 and 17) and regulatory/suppressive CD4+CD25+high T cells (Treg cells)) predict prognosis.1 Interest in the antitumour immune response reached its peak with the results of a French clinical cohort study2 which showed for the first time that the presence of markers for TH1, cytotoxic polarisation and the memory T cells within tumour samples were better predictors of patient survival than the histopathological pTNM (tumour, node, metastases). Several mechanisms interfere with the efficiency of the host’s antitumour immune response in vivo: impairment or loss of the human leucocyte antigen class I-mediated antigen presentation, tumour expression of Fas ligand or B7H1 and B7H4, and altered dendritic cell functions and tumour-derived immunosuppressant molecules (transforming growth factor β (TGFβ), interleukin 10 (IL10), colony-stimulating factor-1 (CSF-1) and vascular endothelial factor (VEGF)).3
T4reg cells represent a heterogeneous group of T cells expressing various cell surface markers and cytokines, which are defined on the basis of their ability to control the activation and function of antigen-reactive T cells, thereby preventing self-reactivity. However, this activity can also …