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

PASCUAL, M; ACLAND,R; PIÑERO,S; PISTORESI, MC; MALETTO, B; MORÓN, G

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencia; 2017

Sociedades de Biociencia

Leukocyte-specific protein 1 (LSP1) is a 52kDa cytoplasmic F-actinbinding phosphoprotein expressed in all human and murine leukocytesas well as in endothelial cells. LSP1 in known as an importantregulator of actin cytoskeleton remodeling. Our group haspreviously shown that Lsp1-/- mice have an impaired CTL responseafter antigen exposure, with Lsp1-/- dendritic cells (DCs) failing toinduce a strong CTL response in vivo, to migrate to lymphoid tissuesand to properly present antigens. To study the role of LSP1in antitumor immune response, we employed the MO5 melanomamodel. WT and Lsp1-/- mice were injected subcutaneously with 105MO5 cells and followed-up until day 26. Tumors in Lsp1-/- mice grewsignificantly faster and bigger than in WT mice (p<0.001). Leukocytepopulations were assessed in tumor, draining lymph node (dLN) andspleen by flow cytometry. In spleen of Lsp1-/- mice we found an increasedfrequency of CD8a+ DCs, CD103+ DCs, CD103+CD8a- DCsand inflammatory monocytes, a decreased frequency of CD8a- DCsand B cells and no difference of T cells and neutrophils. No significantchanges were observed in the frequencies of the same cellpopulations in dLN. No differences were observed in the frequencyof tumor infiltrating leukocytes between Lsp1-/- vs. WT mice. Histologicassessment of tumors in Lsp1-/- mice showed a much smallerintratumoral necrosis as well as lower polymorphonuclear leukocyteinfiltration and higher mononuclear cell infiltration than WT mice.Multivariate statistical analysis of all available data clearly showedthat distribution of leukocyte populations from Lsp1-/- mice is differentto the observed in Lsp1+/+ mice after melanoma implantation.Our hypothesis is that LSP1 deficiency prevents generation of effectiveantitumor immune response in the early moments after MO5 cellimplantation. Functional characterization of tumor infiltrating cells isunder study.