CONICET | Buscador de Institutos y Recursos Humanos

Leukocyte-specificprotein 1 (LSP1) is a 52kDa cytoplasmic F-actin binding phosphoproteinexpressed in all human and murine leukocytes as well as in endothelial cells.LSP1 in known as an important regulator of actin cytoskeleton remodeling. Ourgroup has previously shown that Lsp1-/-mice have an impaired CTL response afterantigen exposure, with Lsp1-/- dendritic cells (DCs) failing to induce a strong CTLresponse in vivo, to migrate to lymphoid tissues and to properly presentantigens. To study the role of LSP1 in antitumor immune response, we employedthe MO5 melanoma model. WT and Lsp1-/-mice were injected subcutaneously with 105 MO5cells and followed-up until day 26. Tumors in Lsp1-/- micegrew significantly faster and bigger than in WT mice (p<0.001). Leukocyte populationswere assessed in tumor, draining lymph node (dLN) and spleen by flow cytometry.In spleen of Lsp1-/- mice we found an increased frequency of CD8a+ DCs,CD103+ DCs, CD103+CD8a- DCs and inflammatory monocytes, a decreased frequencyof CD8a- DCs and B cells and no difference of T cells andneutrophils. No significant changes were observed in the frequencies of the samecell populations in dLN. No differences were observed in the frequency of tumorinfiltrating leukocytes between Lsp1-/-vs. WT mice. Histologic assessment of tumors inLsp1-/- mice showed a much smaller intratumoral necrosis aswell as lower polymorphonuclear leukocyte infiltration and higher mononuclearcell infiltration than WT mice. Multivariate statistical analysis of allavailable data clearly showed that distribution of leukocyte populations fromLsp1-/- mice is different to the observed in Lsp1+/+ miceafter melanoma implantation. Our hypothesis is that LSP1 deficiency preventsgeneration of effective antitumor immune response in the early moments afterMO5 cell implantation. Functionalcharacterization of tumor infiltrating cells is under study.

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