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

Autor: Kohsuke, Isomoto, Koji, Haratani, Takahiro, Tsujikawa, Yusuke, Makutani, Hisato, Kawakami, Masayuki, Takeda, Kimio, Yonesaka, Kaoru, Tanaka, Tsutomu, Iwasa, Hidetoshi, Hayashi, Akihiko, Ito, Kazuto, Nishio, Kazuhiko, Nakagawa
Rok vydání: 2022
Předmět:
Zdroj: Lung Cancer. 174:71-82
ISSN: 0169-5002
Popis: 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 of9 weeks, cohort-B) were enrolled in this retrospective study. The pretreatment TME was evaluated by 16- or 17-color multiplex immunohistochemistry (mIHC)-based spatial profiling at the single-cell level for both cohorts. In cohort-A, changes in the TME after disease progression during ICI treatment were also investigated by mIHC analysis and transcriptomic analysis.Pretreatment tumor tissue from cohort-B manifested poor infiltration of tumor-reactive CD8The presence of intratumoral tumor-reactive CD8
Databáze: OpenAIRE
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