LSP1-DEFICIENT MICE HAVE AN IMPAIRED CONTROL OF MELANOMA TUMOR GROWTH.

PASCUAL, MARÍA MERCEDES; ACLAND STRACK, RACHEL PAOLA; LUQUE, CAROLINA; PIÑERO, SANTIAGO

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Sociedad Argentina de Inmunología

Leukocyte-specific protein 1 (LSP1) is a 52kDa cytoplasmic F-actin binding phosphoprotein expressed in all human and murine leukocytes as well as in endothelial cells. LSP1 in known as an important regulator of actin cytoskeleton remodeling. Our group has previously shown that Lsp1-/- mice have an impaired CTL response after antigen exposure, with Lsp1-/- dendritic cells (DCs) failing to induce a strong CTL response in vivo, to migrate to lymphoid tissues and to properly present antigens. To study the role of LSP1 in antitumor immune response, we employed the MO5 melanoma model. WT and Lsp1-/- mice were injected subcutaneously with 105 MO5 cells and followed-up until day 26. Tumors in Lsp1-/- mice grew significantly faster and bigger than in WT mice (p<0.001). Leukocyte populations were assessed in tumor, draining lymph node (dLN) and spleen by flow cytometry. In spleen of Lsp1-/- mice we found an increased frequency of CD8+ DCs, CD103+ DCs, CD103+CD8- DCs and inflammatory monocytes, a decreased frequency of CD8- DCs and B cells and no difference of T cells and neutrophils. No significant changes were observed in the frequencies of the same cell populations in dLN. No differences were observed in the frequency of tumor infiltrating leukocytes between Lsp1-/- vs. WT mice. Histologic assessment of tumors in Lsp1-/- mice showed a much smaller intratumoral necrosis as well as lower polymorphonuclear leukocyte infiltration and higher mononuclear cell infiltration than WT mice. Multivariate statistical analysis of all available data clearly showed that distribution of leukocyte populations from Lsp1-/- mice is different to the observed in Lsp1+/+ mice after melanoma implantation. Our hypothesis is that LSP1 deficiency prevents generation of effective antitumor immune response in the early moments after MO5 cell implantation. Functional characterization of tumor infiltrating cells is under study.