CD8
CD8 T cell
IL-6
PD-L1
atezolizumab
cancer
checkpoint blockade immunotherapy
clinical trial
interleukin 6
Journal
Cell reports. Medicine
ISSN: 2666-3791
Titre abrégé: Cell Rep Med
Pays: United States
ID NLM: 101766894
Informations de publication
Date de publication:
17 01 2023
17 01 2023
Historique:
received:
21
04
2022
revised:
14
10
2022
accepted:
08
12
2022
pubmed:
5
1
2023
medline:
21
1
2023
entrez:
4
1
2023
Statut:
ppublish
Résumé
Although immune checkpoint inhibitors (ICIs) are established as effective cancer therapies, overcoming therapeutic resistance remains a critical challenge. Here we identify interleukin 6 (IL-6) as a correlate of poor response to atezolizumab (anti-PD-L1) in large clinical trials of advanced kidney, breast, and bladder cancers. In pre-clinical models, combined blockade of PD-L1 and the IL-6 receptor (IL6R) causes synergistic regression of large established tumors and substantially improves anti-tumor CD8
Identifiants
pubmed: 36599350
pii: S2666-3791(22)00442-6
doi: 10.1016/j.xcrm.2022.100878
pmc: PMC9873827
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
atezolizumab
52CMI0WC3Y
B7-H1 Antigen
0
Interleukin-6
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
100878Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests M.A.H., K.Y., L.W., J.E.K., L.L., Y.L., V.G., C.L., D.R., C.O., S.M., S.K., Y.J.C., J.P., Y.S., Z.M., B.B., E.J.F., N.L., H.K., J.Z., M.F., P.W., M.W., I.M., S.J.T., M.M., S.M., L.M., and N.R.W. are employees of Genentech, Inc. M.A.H., K.Y., L.W., J.E.K., L.L., Y.L., P.W., M.M., S.M., L.M., and N.R.W. are inventors on patents related to IL-6. P.S.H. is an employee of Foundation Medicine Inc. K.H. is an employee of Roche Products Ltd. D.F.M. reports a consulting/advisory role for Bristol-Myers Squibb, Merck, Roche/Genentech, Pfizer, Exelixis, Novartis, Eisai, X4 Pharmaceuticals, and Array BioPharma; he also reports that his home institution receives research funding from Prometheus Laboratories. T.P. reports honoraria and consulting/advisory roles with Roche/Genentech, Bristol-Myers Squibb, and Merck; consulting/advisory role with AstraZeneca and Novartis; research funding from AstraZeneca/MedImmune and Roche/Genentech; and other relationships with Ipsen and Bristol-Myers Squibb. L.E. reports honoraria from or consulting/advisory roles with AbbVie, Amgen, AstraZeneca, Bayer, Bristol Meyers Squibb, Celgene, Chugai, eTHeRNA, Genentech, Gritstone, Medimmune, Molecuvax, Macrogenics, Novartis, Peregrine, Replimune, Roche, Silverback, Syndax, and Vaccinex; she reports that her home institution receives funding from Aduro Biotech, AstraZeneca, Breast Cancer Research Foundation, Bristol Meyers Squibb, Corvus, Department of Defense, EMD Serono, Genentech, HeritX, Inc., Maxcyte, Merck, National Cancer Institute, NSABP Foundation, Roche, Tempest, Translational Breast Cancer Research Consortium. J.E.R. has received non-financial support from Roche Genentech and consulting fees from Agensys, Eli Lilly, Sanofi, and Oncogene.
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