Senescence-induced immune remodeling facilitates metastatic adrenal cancer in a sex-dimorphic manner.

ABSTRACT: Aging markedly increases cancer risk, yet our mechanistic understanding of how aging influences cancer initiation is limited. Here we demonstrate that the loss of ZNRF3, an inhibitor of Wnt signaling that is frequently mutated in adrenocortical carcinoma, leads to the induction of cellular senescence that remodels the tissue microenvironment and ultimately permits metastatic adrenal cancer in old animals. The effects are sexually dimorphic, with males exhibiting earlier senescence activation and a greater innate immune response, driven in part by androgens, resulting in high myeloid cell accumulation and lower incidence of malignancy. Conversely, females present a dampened immune response and increased susceptibility to metastatic cancer. Senescence-recruited myeloid cells become depleted

SUBMITTER: Warde KM 

PROVIDER: S-EPMC11534150 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature