Mechanisms of primary and acquired resistance to immune checkpoint inhibitors in advanced non–small cell lung cancer: A multiplex immunohistochemistry–based single-cell analysis

•Resistance mechanisms for immune checkpoint inhibitors (ICIs) were explored.•The tumor immune microenvironment in advanced NSCLC was evaluated in detail by a single-cell spatial profiling with 16 or 17-color multiplex IHC.•Primary ICI resistance was associated with a lack of neoantigen-specific CD8...

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Bibliographic Details
Published in:Lung cancer (Amsterdam, Netherlands) Netherlands), 2022-12, Vol.174, p.71-82
Main Authors: Isomoto, Kohsuke, Haratani, Koji, Tsujikawa, Takahiro, Makutani, Yusuke, Kawakami, Hisato, Takeda, Masayuki, Yonesaka, Kimio, Tanaka, Kaoru, Iwasa, Tsutomu, Hayashi, Hidetoshi, Ito, Akihiko, Nishio, Kazuto, Nakagawa, Kazuhiko
Format: Article
Language:English
Subjects:
Acquired resistance
Carcinoma, Non-Small-Cell Lung - pathology
CD8-Positive T-Lymphocytes
Disease Progression
Humans
Immune checkpoint inhibitor
Immune Checkpoint Inhibitors - pharmacology
Immune Checkpoint Inhibitors - therapeutic use
Lung Neoplasms - pathology
Multiplex immunohistochemistry
Non–small cell lung cancer
Primary resistance
Retrospective Studies
Single-Cell Analysis
Tumor immune microenvironment
Tumor Microenvironment
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Summary:•Resistance mechanisms for immune checkpoint inhibitors (ICIs) were explored.•The tumor immune microenvironment in advanced NSCLC was evaluated in detail by a single-cell spatial profiling with 16 or 17-color multiplex IHC.•Primary ICI resistance was associated with a lack of neoantigen-specific CD8+ TILs.•Acquired resistance was related to MDSC infiltration, neoepitope loss, and other features. Immune checkpoint inhibitors (ICIs) have become a key therapeutic modality for advanced non–small cell lung cancer (NSCLC), but most patients experience primary or acquired resistance to these drugs. We here explored the mechanisms underlying both types of ICI resistance by analysis of the tumor immune microenvironment (TME). Four patients who experienced a long-term response to ICI treatment (progression-free survival [PFS] of ≥12 months) followed by disease progression, after which a rebiopsy was immediately performed (cohort-A), as well as four patients who experienced early tumor progression during ICI treatment (PFS of
ISSN:0169-5002
1872-8332
DOI:10.1016/j.lungcan.2022.10.012