LSP1 KO TUMOR-BEARING MICE HAVE A HIGHER FREQUENCY OF FUNCTIONAL CROSS-PRESENTING DENDRITIC CELLS IN THE SPLEEN.

Mar del Plata

Congreso; LXVI Reunión Anual de la Sociedad Argentina de Inmunología (SAI); 2018

Sociedad Argentina de Inmunología

All leukocytes and endothelial cells from human and mice express a 52kDa cytoplasmic F-actin binding phosphoprotein, called Leukocyte-specific protein 1 (LSP1). This protein is known as an important actin cytoskeleton-regulator. LSP1 polymorphisms or downregulation are considered risk factors for some types of cancer. Using the MO5 melanoma model, our group has shown that LSP1 deficient mice have an impaired control of melanoma growth. In order to study the role of LSP1 in antitumor immune response, WT and Lsp1-/- mice were subcutaneously-injected with 105 MO5 cells and followed-up until day 15 or 17 depending on the experiment. At these time points, tumors in Lsp1-/- mice were bigger than in WT controls (p<0.01). Taking into account that the MO5 cell line expresses OVA, tumoral-antigen presentation was assessed in vitro using the H2-Kb-restricted OVA257-264-specific CD8+ T cell hybridoma (B3Z). We observed a higher tumoral-antigen presentation when B3Z cells were incubated with CD11c+ splenocytes harvested from LSP1 KO tumor-bearing mice than from WT tumor-bearing mice (p<0.0001). This could be a result of a higher proportion of cross-presenting DCs in LSP1 KO spleen compared to WT (CD8+ DCs p<0.0001; CD103+ DCs p<0.01). However, no difference in tumor-antigen presentation was found after tumor draining lymph node (dLN) analysis, despite the lower proportion of CD8+ DCs and higher proportion of CD8- CD103- DCs in LSP1 KO dLN compared to WT (p<0.01). Flow cytometry analysis also revealed a higher frequency of monocytes and a lower frequency of CD11chi cells in LSP1 KO spleen (p<0.001 and p<0.01 respectively). We hypothesize that cross-presenting DCs accumulate in spleen of lsp1-/- mice hindering their action into tumors and resulting in an impaired control of melanoma growth.