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

MERCEDES PASCUAL; NICOLAS DANIEL DHO; MARÍA INÉS CRESPO; MARÍA C PISTORESI- PALENCIA; BELKYS A. MALETTO; G MORON

Buenos Aires

Congreso; LXVIII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI); 2020

SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI)

Leukocyte-specific protein 1 (LSP1) is a 52kDa cytoplasmic F-actinbinding phosphoprotein expressed in all human and murine leukocytesas well as in endothelial cells. This protein in known as animportant regulator of actin cytoskeleton remodeling. LSP1 polymorphismsor downregulation are considered risk factors for some typesof cancer.In order to study the role of LSP1 in antitumor immune response, weemployed the B16-OVA melanoma model.We previously shown that B16-OVA tumor in Lsp1-/- mice grow significantlyfaster and bigger than in wild type (WT) controls. Also, tumorsharvested from Lsp1-/- mice show a lower frequency of totalinfiltrating leukocytes compared to WT mice.Considering that LSP1 is expressed by leukocytes and endothelialcells, 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 adoptivelytransferred into WT or Lsp1-/- tumor-bearing mice. We observed alower frequency of Lsp1-/- migrant leukocytes in tumors developedin WT and Lsp1-/- mice (p<0.01 and p<0.001 respectively) 48hr aftertransfection. However, no difference in migrant cells was foundwhen tumor draining lymph nodes (dLN) were analyzed.Taking into account CD8+ T cells priming importance in antitumorimmunity, an in vivo proliferation assay was performed, by transferringCD8+ T cells from OT I mice to WT and Lsp1-/- tumor-bearingmice. Transferred CD8+ T cells failed to proliferate in Lsp1-/- dLNcompared to WT dLN 48hr after cell transference (p<0.01). Additionally,we observed that transferred CD8+ T cells in Lsp1-/- micedisplayed a significantly lower activation pattern as measured byexpression of CD69 and CD44 (p<0.01).We hypothesize that the impaired control of melanoma growth inLsp1-/- mice could be caused, by a reduced extravasation efficiencyof Lsp1-/- leukocytes, combined with a defective CD8+ T cells primingin Lsp1-/- tumor dLN.