Cancer immune control needs senescence induction by interferon-dependent cell cycle regulator pathways in tumours.

ABSTRACT: Immune checkpoint blockade (ICB)-based or natural cancer immune responses largely eliminate tumours. Yet, they require additional mechanisms to arrest those cancer cells that are not rejected. Cytokine-induced senescence (CIS) can stably arrest cancer cells, suggesting that interferon-dependent induction of senescence-inducing cell cycle regulators is needed to control those cancer cells that escape from killing. Here we report in two different cancers sensitive to T cell-mediated rejection, that deletion of the senescence-inducing cell cycle regulators p16^Ink4a/p19^Arf (Cdkn2a) or p21^Cip1 (Cdkn1a) in the tumour cells abrogates both the natural and the ICB-induced cancer immune control. Also in humans, melanoma metastases that progressed rapidly during ICB h

SUBMITTER: Brenner E 

PROVIDER: S-EPMC7067802 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature