Inhibition of estrogen signaling in myeloid cells increases tumor immunity in melanoma.

ABSTRACT: Immune checkpoint blockade (ICB) therapies have significantly prolonged patient survival across multiple tumor types, particularly in melanoma. Interestingly, sex-specific differences in response to ICB have been observed, with males receiving a greater benefit from ICB than females, although the mechanism or mechanisms underlying this difference are unknown. Mining published transcriptomic data sets, we determined that the response to ICBs is influenced by the functionality of intratumoral macrophages. This puts into context our observation that estrogens (E2) working through the estrogen receptor α (ERα) stimulated melanoma growth in murine models by skewing macrophage polarization toward an immune-suppressive state that promoted CD8+ T cell dysfunction and exhaustion and ICB resistance.

SUBMITTER: Chakraborty B 

PROVIDER: S-EPMC8631601 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature