26.    Intrinsic role of galectin-1 in the control of the functional properties of immune                  cells in a prostate cancer context

The identification of effective new therapies for prostate cancer requires a better understanding of the multiple molecular interactions between tumor cells and their associated stroma. In this context, Galectin-1 (Gal-1) plays a major role determining the properties of the prostatic carcinoma microenvironment. The aim of this study
was to elucidate whether Gal-1, in addition to promote tumor neoangiogenesis and immune regulations, plays an additional role as an intrinsic regulator of CD8+ T cell function. To address this, we used two approaches: an in vitro T cell polyclonal activation model, combining different cell types (purified by cell sorting) in a prostate
tumor microenvironment and an adoptive transfer of Gal-1 deficient Lgals1-/- (KO) and wild type (WT) cells into immunodeficient mice. The in vitro combination of KO and WT cells, allowed us to elucidate how the endogenous Gal-1 of each cellular compartment impacts on the CD8+ T cell proliferation and citotoxicity. The absence
of Gal-1 in antigen presenting cells did not significantly modify any function of CD8+T cells. Conversely, the absence of Gal-1 in CD4+ T cells induced a 1.21 fold increase in the proliferation of CD8+T cells. However, the most significant difference in the proliferation was obtained by absence of intrinsic Gal-1 in the CD8+ T cells
themselves (2.12). We further evaluated whether Gal-1 is relevant for effector function. Our results demonstrated that upon activation, KO T cells have increased their ability to degranulate (evaluated as % (1.87 fold) and the content of granules (2.48 fold increase) (p <0.05, t test Student). We then compared the in vivo tumor growth in nude mice adoptively reconstituted with Gal1 KO or WT immune systems: the presence of KO immune cells increased for 24.1 days the lag time and 30% on the tumor duplication time. These results demonstrate that Gal-1 modulates the intrinsic function of lymphocytes in a prostate cancer context.