Absence of TNFR1 enhances infiltration of CD4+/CD8+ T-lymphocytes in the tumor microenvironment reducing subcutaneous melanoma growth.

RODRIGUEZ Y; CASTRO M; CAMPOS L; DELLA VEDOVA M; RAMIREZ, DC; CROCI D; ALVAREZ SE

Congreso; SAIC 2016; 2016

A tumor is not simply a mass of genetically modified and identical cells. Neoplastic cells are in close interaction with endothelial, stromal and immune cells by both cell-cell contact and soluble factors in the tumor microenvironment. The participation of natural killer (NK) cells, CD4+ and CD8+ T lymphocytes (TL) and M1 pro-inflammatory macrophages are determinant in cancer regression. However, tumor cells have mechanisms to evade the immune response and modulate the microenvironment allowing the establishment of cell phenotypes that promote tumor growth, invasion and metastasis. Thus, the tumor microenvironment has a crucial role in cancer progression. Indeed, in a model of subcutaneous implantation of B16F1 murine melanoma cells, we have previously shown a diminished tumor growth in tumor necrosis alpha receptor 1 (TNFR1)-KO mice compared to wild type (WT) mice. Here, we aimed to establish the role of immune cells and cytokines in this differential response. The number of M2-like tumor associated macrophages (TAMs; F4/80+ CD206+) and lymphocytic infiltrate (CD4+ CD8+ LT) was evaluated by flow cytometry in tumor samples collected 19 days after inoculation of B16F1 cells. In addition, we estimated CCL-2 and IL-10 levels by QPCR and ELISA respectively. Although expression of CCL-2 (chemokine involved in macrophage recruitment) was significantly higher in tumor tissue from TNFRI-KO mice, no differences in the number or TAMs were observed. Furthermore, reduced levels of IL-10 in TNFRI KO mice were accompanied by a significantly higher lymphocytic infiltrate CD4+ and CD8+. Altogether, these data indicates that absence of TNFRI in C57BL/6 mice enhances antitumor immune responses leading to diminished tumor growth.