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Brenner, E.* ; Schörg, B.F.* ; Ahmetlic, F. ; Wieder, T.* ; Hilke, F.J.* ; Simon, N.* ; Schroeder, C.* ; Demidov, G.* ; Riedel, T.* ; Fehrenbacher, B.* ; Schaller, M.* ; Forschner, A.* ; Eigentler, T.* ; Niessner, H.* ; Sinnberg, T.* ; Böhm, K.S.* ; Hömberg, N. ; Braumüller, H.* ; Dauch, D.* ; Zwirner, S.* ; Zender, L.* ; Sonanini, D.* ; Geishauser, A. ; Bauer, J.* ; Eichner, M.* ; Jarick, K.J.* ; Beilhack, A.* ; Biskup, S.* ; Döcker, D.* ; Schadendorf, D.* ; Quintanilla-Martinez, L.* ; Pichler, B.J.* ; Kneilling, M.* ; Mocikat, R. ; Röcken, M.*

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

Nat. Commun. 11:1335 (2020)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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 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 cancer cells that escape from eradication.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Cd4(+) T-cells; Pd-1 Blockade; Checkpoint Blockade; Immunotherapy; Melanoma; Resistance; Rna; Surveillance; Mechanisms; Responses
Language english
Publication Year 2020
HGF-reported in Year 2020
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 11, Issue: 1, Pages: , Article Number: 1335 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) AG Translationale Molekulare Immunologie (TMI)
Institute of Molecular Immunology (IMI)
POF-Topic(s) 30203 - Molecular Targets and Therapies
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s) Immune Response and Infection
PSP Element(s) G-501711-001
G-501700-006
DOI 10.1038/s41467-020-14987-6
WOS ID WOS:000563526500001
Scopus ID 85081715323
PubMed ID 32165639
Erfassungsdatum 2020-04-23
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