Targetable mechanisms driving immunoevasion of persistent senescent cells link chemotherapy-resistant cancer to aging.

ABSTRACT: Cellular senescence is a tumor suppressive mechanism that can paradoxically contribute to aging pathologies. Despite evidence of immune clearance in mouse models, it is not known how senescent cells (SnCs) persist and accumulate with age or in tumors in individuals. Here, we identify cooperative mechanisms that orchestrate the immunoevasion and persistence of normal and cancer human SnCs through extracellular targeting of natural killer receptor signaling. Damaged SnCs avoid immune recognition through MMPs-dependent shedding of NKG2D-ligands reinforced via paracrine suppression of NKG2D receptor-mediated immunosurveillance. These coordinated immunoediting processes are evident in residual, drug-resistant tumors from cohorts of >700 prostate and breast cancer patients treated with senescenc

SUBMITTER: Munoz DP 

PROVIDER: S-EPMC6675550 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature