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

PASCUAL, MARÍA MERCEDES; DHO, NICOLÁS DANIEL; ACLAND STRACK, RACHEL PAOLA; CRESPO, MARÍA INÉS; PISTORESI, MARÍA CRISTINA; MALETTO, BELKYS ANGÉLICA; MORÓN, VÍCTOR GABRIEL

Mar del Plata

Congreso; REUNIÓN SAI-SAIC-SAFIS; 2018

All leukocytes and endothelial cells from human and mice expressa 52kDa cytoplasmic F-actin binding phosphoprotein, calledLeukocyte-specific protein 1 (LSP1). This protein is known as animportant actin cytoskeleton-regulator. LSP1 polymorphisms ordownregulation are considered risk factors for some types of cancer.Using the MO5 melanoma model, our group has shown thatLSP1 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 105MO5cells and followed-up until day 15 or 17 depending on the experiment.At these time points, tumors in Lsp1-/- mice were bigger thanin WT controls (p<0.01). Taking into account that the MO5 cellline expresses OVA, tumoral-antigen presentation was assessedin vitro using the H2-Kb-restricted OVA257-264-specific CD8+T cell hybridoma (B3Z). We observed a higher tumoral-antigenpresentation when B3Z cells were incubated with CD11c+ splenocytesharvested from LSP1 KO tumor-bearing mice than from WTtumor-bearing mice (p<0.0001). This could be a result of a higherproportion of cross-presenting DCs in LSP1 KO spleen comparedto WT (CD8α+ DCs p<0.0001; CD103+ DCs p<0.01). However, nodifference in tumor-antigen presentation was found after tumordraining lymph node (dLN) analysis, despite the lower proportionof CD8α+ DCs and higher proportion of CD8α- CD103- DCs in LSP1KO dLN compared to WT (p<0.01). Flow cytometry analysis alsorevealed a higher frequency of monocytes and a lower frequency ofCD11chi cells in LSP1 KO spleen (p<0.001 and p<0.01 respectively).We hypothesize that cross-presenting DCs accumulate in spleenof lsp1-/- mice hindering their action into tumors and resulting in animpaired control of melanoma growth.