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The role of sex in the innate and adaptive immune environment of metastatic colorectal cancer

2020; Springer Nature; Volume: 123; Issue: 4 Linguagem: Inglês

10.1038/s41416-020-0913-8

1532-1827

Anita L. Ray, Robert A. Nofchissey, Maaz Khan, Megan A. Reidy, Megan R. Lerner, Xiangyan Wu, Shaoxuan Guo, Spencer L. Hill, Nathaniel Weygant, Sarah F. Adams, Eliseo F. Castillo, William L. Berry, Michael B. Stout, Katherine T. Morris,

Immune Cell Function and Interaction

Women with colorectal cancer (CRC) have a significant survival advantage over men. Sex influences on the tumour microenvironment (TME) are not well characterised, despite the importance of immune response in CRC. We hypothesised that sex-divergent immune responses could contribute to survival.Using a murine model of metastatic CRC, we examined T cells, macrophages, and cytokines locally and systemically. TME and serum cytokines were measured by multiplex bead-based arrays, while FCA was used to identify cells and phenotypes. IHC provided spatial confirmation of T cell infiltration.Females had increased survival and T cell infiltration. CD8, CD4 and Th2 populations correlated with longer survival. Males had increased serum levels of chemokines and inflammation-associated cytokines. Within the TME, males had lower cytokine levels than females, and a shallower cytokine gradient to the periphery. Female tumours had elevated IL-10+ macrophages, which correlated with survival.These data demonstrate survival-associated differences in the immune response of males and females to metastatic CRC. Females showed changes in cytokine production accompanied by increased immune cell populations, biased toward Th2-axis phenotypes. Key differences in the immune response to CRC correlated with survival in this model. These differences support a multi-faceted shift across the TME.