Distinct Immune Cell Populations Define Response to Anti-PD-1 Monotherapy and Anti-PD-1/Anti-CTLA-4 Combined Therapy

Distinct Immune Cell Populations Define Response to Anti-PD-1 Monotherapy and Anti-PD-1/Anti-CTLA-4 Combined Therapy.

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1016/j.ccell.2019.01.003
Journal or Publication Title: Cancer Cell
Volume: 35
Number: 2
Page Range: 238-255.e6
Date: 2019
Divisions: Human Viral and Cancer Immunology
Depositing User: General Admin
Identification Number: 10.1016/j.ccell.2019.01.003
ISSN: 15356108
Date Deposited: 17 Dec 2020 02:51
Abstract:

Cancer immunotherapies provide survival benefits in responding patients, but many patients fail to respond. Identifying the biology of treatment response and resistance are a priority to optimize drug selection and improve patient outcomes. We performed transcriptomic and immune profiling on 158 tumor biopsies from melanoma patients treated with anti-PD-1 monotherapy (n = 63) or combined anti-PD-1 and anti-CTLA-4 (n = 57). These data identified activated T cell signatures and T cell populations in responders to both treatments. Further mass cytometry analysis identified an EOMES+CD69+CD45RO+ effector memory T cell phenotype that was significantly more abundant in responders to combined immunotherapy compared with non-responders (n = 18). The gene expression profile of this population was associated with longer progression-free survival in patients treated with single agent and greater tumor shrinkage in both treatments.

Keywords: EOMES; RNA-seq; anti-CTLA-4; anti-PD-1; combination therapy; immune checkpoint inhibitors; immunotherapy; melanoma; predictive biomarkers; resistance mechanisms.

Copyright © 2019 Elsevier Inc. All rights reserved.

Creators:
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Gide, Tuba N.
UNSPECIFIED
Quek, Camelia
UNSPECIFIED
Menzies, Alexander M.
UNSPECIFIED
Tasker, Annie T.
UNSPECIFIED
Shang, Ping
UNSPECIFIED
Holst, Jeff
UNSPECIFIED
Madore, Jason
UNSPECIFIED
Lim, Su Yin
UNSPECIFIED
Velickovic, Rebecca
UNSPECIFIED
Wongchenko, Matthew
UNSPECIFIED
Yan, Yibing
UNSPECIFIED
Lo, Serigne
UNSPECIFIED
Carlino, Matteo S.
UNSPECIFIED
Guminski, Alexander
UNSPECIFIED
Saw, Robyn P.M.
UNSPECIFIED
Pang, Angel
UNSPECIFIED
McGuire, Helen M.
UNSPECIFIED
Palendira, Umaimainthan
UNSPECIFIED
Thompson, John F.
UNSPECIFIED
Rizos, Helen
UNSPECIFIED
Silva, Ines Pires da
UNSPECIFIED
Batten, Marcel
UNSPECIFIED
Scolyer, Richard A.
UNSPECIFIED
Long, Georgina V.
UNSPECIFIED
Wilmott, James S.
UNSPECIFIED
Last Modified: 17 Dec 2020 02:51
URI: https://eprints.centenary.org.au/id/eprint/282

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