Abstract / Summary
Abstract Sex-based differences in colorectal cancer (CRC) incidence and progression are well-established, yet their underlying immunological mechanisms remain insufficiently understood. In this study, we characterized and compared systemic and tumor-associated immune responses in male and female mice using the azoxymethane/dextran sodium sulfate (AOM/DSS) model of CRC. At a macroscopic level, males develop greater numbers and larger tumors. In line with this, the histopathological analysis shows that neoplastic tissue is more abundant in males. In contrast, flow cytometric analysis revealed that male mice exhibited increased intratumoral γδ T cells and tumor-associated macrophages, accompanied by increased MCP-1 compared with females. In contrast, females demonstrated a stronger cellular response with a higher infiltrate of cytotoxic lymphocytes, B cells, and plasmatic cells. In concordance, systemically, males exhibit a higher percentage of T γ δ lymphocytes in the spleen and an increase in MCP-1 in serum, while females have a higher level of CD8 + in the mesenteric ganglia. In summary, these results show a stronger cellular response by females in nearby tissues and in the tumor. Also, suggest that males have a worse prognosis due to the infiltration of macrophages and γδ T cells, and the pro-tumoral action of MCP-1.