Clinical and molecular features of acquired resistance to immunotherapy in non-small cell lung cancer
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved..
Although immunotherapy with PD-(L)1 blockade is routine for lung cancer, little is known about acquired resistance. Among 1,201 patients with non-small cell lung cancer (NSCLC) treated with PD-(L)1 blockade, acquired resistance is common, occurring in >60% of initial responders. Acquired resistance shows differential expression of inflammation and interferon (IFN) signaling. Relapsed tumors can be separated by upregulated or stable expression of IFNγ response genes. Upregulation of IFNγ response genes is associated with putative routes of resistance characterized by signatures of persistent IFN signaling, immune dysfunction, and mutations in antigen presentation genes which can be recapitulated in multiple murine models of acquired resistance to PD-(L)1 blockade after in vitro IFNγ treatment. Acquired resistance to PD-(L)1 blockade in NSCLC is associated with an ongoing, but altered IFN response. The persistently inflamed, rather than excluded or deserted, tumor microenvironment of acquired resistance may inform therapeutic strategies to effectively reprogram and reverse acquired resistance.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:42 |
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| Enthalten in: |
Cancer cell - 42(2024), 2 vom: 12. Feb., Seite 209-224.e9 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Memon, Danish [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 15.02.2024 Date Revised 13.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ccell.2023.12.013 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 245 | 1 | 0 | |a Clinical and molecular features of acquired resistance to immunotherapy in non-small cell lung cancer |
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| 500 | |a Date Completed 15.02.2024 | ||
| 500 | |a Date Revised 13.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Although immunotherapy with PD-(L)1 blockade is routine for lung cancer, little is known about acquired resistance. Among 1,201 patients with non-small cell lung cancer (NSCLC) treated with PD-(L)1 blockade, acquired resistance is common, occurring in >60% of initial responders. Acquired resistance shows differential expression of inflammation and interferon (IFN) signaling. Relapsed tumors can be separated by upregulated or stable expression of IFNγ response genes. Upregulation of IFNγ response genes is associated with putative routes of resistance characterized by signatures of persistent IFN signaling, immune dysfunction, and mutations in antigen presentation genes which can be recapitulated in multiple murine models of acquired resistance to PD-(L)1 blockade after in vitro IFNγ treatment. Acquired resistance to PD-(L)1 blockade in NSCLC is associated with an ongoing, but altered IFN response. The persistently inflamed, rather than excluded or deserted, tumor microenvironment of acquired resistance may inform therapeutic strategies to effectively reprogram and reverse acquired resistance | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Clonal selection | |
| 650 | 4 | |a Genomics and Transcriptomics | |
| 650 | 4 | |a Immune escape | |
| 650 | 4 | |a Immune-checkpoint blockade | |
| 650 | 4 | |a Interferon alpha/gamma response | |
| 650 | 4 | |a Neoantigens | |
| 650 | 4 | |a T cell exhaustion | |
| 650 | 4 | |a Tumor heterogeneity | |
| 650 | 4 | |a Type I and Type II Interferons | |
| 650 | 4 | |a anti-PD-1 therapy | |
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| 700 | 1 | |a Schoenfeld, Adam J |e verfasserin |4 aut | |
| 700 | 1 | |a Ye, Darwin |e verfasserin |4 aut | |
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| 700 | 1 | |a Rizvi, Hira |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xiang |e verfasserin |4 aut | |
| 700 | 1 | |a Keddar, Mohamed Reda |e verfasserin |4 aut | |
| 700 | 1 | |a Mathew, Divij |e verfasserin |4 aut | |
| 700 | 1 | |a Yoo, Kyung Jin |e verfasserin |4 aut | |
| 700 | 1 | |a Qiu, Jingya |e verfasserin |4 aut | |
| 700 | 1 | |a Lihm, Jayon |e verfasserin |4 aut | |
| 700 | 1 | |a Miriyala, Jayalaksmi |e verfasserin |4 aut | |
| 700 | 1 | |a Sauter, Jennifer L |e verfasserin |4 aut | |
| 700 | 1 | |a Luo, Jia |e verfasserin |4 aut | |
| 700 | 1 | |a Chow, Andrew |e verfasserin |4 aut | |
| 700 | 1 | |a Bhanot, Umesh K |e verfasserin |4 aut | |
| 700 | 1 | |a McCarthy, Caroline |e verfasserin |4 aut | |
| 700 | 1 | |a Vanderbilt, Chad M |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Cailian |e verfasserin |4 aut | |
| 700 | 1 | |a Abu-Akeel, Mohsen |e verfasserin |4 aut | |
| 700 | 1 | |a Plodkowski, Andrew J |e verfasserin |4 aut | |
| 700 | 1 | |a McGranahan, Nicholas |e verfasserin |4 aut | |
| 700 | 1 | |a Łuksza, Marta |e verfasserin |4 aut | |
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| 700 | 1 | |a Merghoub, Taha |e verfasserin |4 aut | |
| 700 | 1 | |a Achour, Ikbel |e verfasserin |4 aut | |
| 700 | 1 | |a Barrett, J Carl |e verfasserin |4 aut | |
| 700 | 1 | |a Stewart, Ross |e verfasserin |4 aut | |
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| 700 | 1 | |a Schreiber, Taylor H |e verfasserin |4 aut | |
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| 700 | 1 | |a Miller, Martin L |e verfasserin |4 aut | |
| 700 | 1 | |a Hellmann, Matthew D |e verfasserin |4 aut | |
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