20016 Background: CD161 is a glycoprotein expressed in >90% of NK and 25% of T cells in the peripheral blood of healthy individuals. Several NK receptors on T cells infiltrating tumors have been proven to negatively influence their effector function and therefore play a role in tumor escape. In this study, we investigated T cells expressing CD161 in the peripheral blood mononuclear cells (PBMC), tumor infiltrarting lymphocytes (TIL) or malignant effusions (ME) from patients with several types of cancer. Methods: Expression of CD161 in CD4+ or CD8+ (lacking CD56) T cells, was examined using four-colour flow cytometry. The proliferative capacity and potential cytokine production of purified CD4+CD161+CD56− cells, were studied after weak or strong stimulation, with or without costimulation, in the presence or absence of Interleukin-2 (IL-2). The possible regulatory function of activated CD4+CD161+CD56− cells on T cell allo-responses was also investigated. Results: CD4+CD161+CD56− T cells were significantly increased (P < 0.01) in TIL, either from tumor tissue (n = 8) or metastatic lymph nodes (n = 5), and ME (n = 25), compared to PBMC from both cancer patients (n = 36) and healthy individuals (n = 12). CD4+CD161+CD56− cells from all sources tested, have the same phenotypic characteristics: they comprise a memory T cell population (CD45RO+CD45RA−) expressing high CD28 and CD95 and low CD25, CD38 and HLA-DR. Co-stimulation via CD28 is important for induction of proliferation and production of large amounts of Th1 and Th2 cytokines (IFN-γ, TNF-a, GM-CSF, IL-4 and IL-10). Following co-stimulation, CD4+CD161+CD56− cells also exert a suppressive activity on autologous PBMC allo-responses. The latter effect does not require cell-to-cell contact and is mediated by soluble factors, including IL10, since neutralization of IL10 partially restored the immune response. Conclusions: CD4+CD161+CD56− cells represent a distinct memory T cell population that is significantly increased in TIL and ME in patients with cancer. These cells are capable of secreting large amounts of both Th1 and Th2 cytokines and might play an immunosuppressive role, mainly through IL-10 production, depending on the microenvironment in which they develop. No significant financial relationships to disclose.
Identification of a novel human memory T-cell population with the characteristics of stem-like chemo-resistance