IMPAIRED ANTITUMOR IMMUNITY IN LSP1-/- MICE IS ACCOMPANIED BY AN INTRATUMORAL CYTOKINE DISBALANCE

PASCUAL, MARÍA MERCEDES; DHO, NICOLÁS DANIEL; CRESPO, MARÍA INÉS; PISTORESI, MARÍA CRISTINA; MALETTO, BELKYS A; MORÓN, GABRIEL

Congreso; Reunión Conjunta SAI - SAIC - AAFE - NANOMED.AR 2021; 2021

Sociedad Argentina de Inmunología

Leukocyte-specific protein 1 (LSP1) is a 52kDa cytoplasmic F-actin binding phosphoprotein expressed in all human and murine leuko cytes 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 typesof cancer. We previously shown that B16-OVA melanoma in Lsp1-/- mice grows 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. Furthermore, there is a reduced extravasation efficiency of Lsp1-/- leukocytes into tumor, combined with a defective CD8+ T cell priming in Lsp1-/- tumor dLN.We continued this study by comparing the cytokine milieu in melanoma tumors in Lsp1-/- vs WT mice. For that, 1.105 B16-OVA melanoma cells were implanted in both animal groups and on day 16 tumors were harvested. Aproximately 70 mg tumor/mouse was digested using T-PER™ Tissue Protein Extraction Reagent added with protease inhibitor. Tumor-cytokine content was determined by a multiplex commercial assay using fluorescence–encoded beads that allows simultaneous quantification of 13 mouse cytokines including IL-1α, IL-1β, IL-6, IL-10, IL-12p70, IL-17A, IL-23, IL-27, MCP-1, IFN-β, IFN-γ, TNF-α and GM-CSF. We found that tumors in Lsp1-/- mice have significantly higher levels of IL-1β, IL-10, IL-27, IL-17A and IL23 (p<0.01) as well as higher levels of TNF-α, IL-12p70, IFN-β and GM-CSF (p<0.001) than WT mice. However, tumor extracts contained similar levels of IL-1α, INF-γ, MCP-1 and IL-6. Sumarizing, the tumoral milieu in Lsp1-/- mice has increased levels of cytokines that can act as angiogenesis promoters, favoring tumoral growth and chronic inflammation, as well as cytokines involved in promoting DC activation.