- REDUCED EXTRAVASATION EFFICIENCY OF LSP1-/- LEUKOCYTES COMBINED WITH A DEFECTIVE CD8+ T CELLS PRIMING IN LSP1-/- TUMOR DRAINING LYMPH NODE CAUSED AN IMPAIRED ANTITUMOR IMMUNITY RESPONSE IN LSP1-/- MICE

Congreso Virtual

Congreso; Reunión Anual de Sociedades de Biociencias; 2020

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. This protein in known as an important regulator of actin cytoskeleton remodeling. LSP1 polymorphisms or downregulation are considered risk factors for some types of cancer.In order to study the role of LSP1 in antitumor immune response, we employed the B16-OVA melanoma model. We previously shown that B16-OVA tumor in Lsp1-/- mice grow significantly faster and bigger than in wild type (WT) controls. Also, tumors harvested from Lsp1-/- mice show a lower frequency of total infiltrating leukocytes compared to WT mice. Considering that LSP1 is expressed by leukocytes and endothelial cells, an in vivo migration assay was performed. WT and Lsp1-/- splenocytes were labeled with Cell Proliferation Dye eFluor 670 (3µM and 0.3µM respectively), mixed in a 1:1 ratio and adoptively transferred into WT or Lsp1-/- tumor-bearing mice. We observed a lower frequency of Lsp1-/- migrant leukocytes in tumors developed in WT and Lsp1-/- mice (p<0.01 and p<0.001 respectively) 48hr after transfection. However, no difference in migrant cells was found when tumor draining lymph nodes (dLN) were analyzed.Taking into account CD8+ T cells priming importance in antitumor immunity, an in vivo proliferation assay was performed, by transferring CD8+ T cells from OT I mice to WT and Lsp1-/- tumor-bearing mice. Transferred CD8+ T cells failed to proliferate in Lsp1-/- dLN compared to WT dLN 48hr after cell transference (p<0.01). Additionally, we observed that transferred CD8+ T cells in Lsp1-/- mice displayed a significantly lower activation pattern as measured by expression of CD69 and CD44 (p<0.01).We hypothesize that the impaired control of melanoma growth in Lsp1-/- mice could be caused, by a reduced extravasation efficiency of Lsp1-/- leukocytes, combined with a defective CD8+ T cells priming in Lsp1-/- tumor dLN.