Cancer immune control needs senescence induction by Stat1 dependent cell cycle regulator pathways in tumours

Immune checkpoint bloackade (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, we show that deletion of the senescence-inducing cell cycle regulators p16Ink4a/p19Arf (Cdkn2a) or p21Cip1 (Cdkn1a) in the tumour cells abrogated both, the natural and the ICB-induced cancer immune control. Also in humans, melanoma metastases that progressed rapidly during ICB have losses of senescence-inducing genes and amplifications of senescence inhibitors. Metastatic cells also resist CIS. Such genetic and functional alterations are infrequent in metastatic melanomas regressing during ICB. Thus, activation of tumour-intrinsic, senescence-inducing cell cycle regulators is required to stably arrest those cancer cells that escape from eradication.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 1 Publication

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001005778	Aligned BAM files from NextSeq500 tageted panel sequencing of 84 samples from matched tumour-normal pairs of 42 melanoma patients. The dataset consists of 30 non-responders and 12 responders to ICB.	NextSeq 500	84

Publications	Citations
Cancer immune control needs senescence induction by interferon-dependent cell cycle regulator pathways in tumours. Brenner E, Schörg BF, Ahmetlić F, Wieder T, Hilke FJ, Simon N, Schroeder C, Demidov G, Riedel T, Fehrenbacher B, Schaller M, Forschner A, Eigentler T, Niessner H, Sinnberg T, Böhm KS, Hömberg N, Braumüller H, Dauch D, Zwirner S, Zender L, Sonanini D, Geishauser A, Bauer J, Eichner M, Jarick KJ, Beilhack A, Biskup S, Döcker D, Schadendorf D, Quintanilla-Martinez L, Pichler BJ, Kneilling M, Mocikat R, Röcken M. Nat Commun 11: 2020 1335	55

Publications

Citations

Cancer immune control needs senescence induction by interferon-dependent cell cycle regulator pathways in tumours.
Brenner E, Schörg BF, Ahmetlić F, Wieder T, Hilke FJ, Simon N, Schroeder C, Demidov G, Riedel T, Fehrenbacher B, Schaller M, Forschner A, Eigentler T, Niessner H, Sinnberg T, Böhm KS, Hömberg N, Braumüller H, Dauch D, Zwirner S, Zender L, Sonanini D, Geishauser A, Bauer J, Eichner M, Jarick KJ, Beilhack A, Biskup S, Döcker D, Schadendorf D, Quintanilla-Martinez L, Pichler BJ, Kneilling M, Mocikat R, Röcken M. Nat Commun 11: 2020 1335