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전남대학교 의과대학, 화순전남대학교병원

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Exp. Mol. Med., May 01 2025, | https://doi.org/10.1038/s12276-025-01448-7 Progressive accumulation of circulating CD27-CD28- effector/memory CD8+ T cells in patients with lung cancer blunts responses to immune checkpoint inhibitor therapy

Sung-Woo Lee^1,2,8, Ju Sik Yun ^3,8, Young Ju Kim ^1,2,4,5, Saei Jeong ^1,2,4,5, Jeong Eun Noh ^1,2,4,5, Hee-Ok Kim ⁶, Hyun-Ju Cho ⁷, Cheol-Kyu Park ⁷, In-Jae Oh ^7,* and Jae-Ho Cho ^1,2,4,5,*

¹Department of Microbiology and Immunology, Chonnam National University Medical School, Gwangju, Republic of Korea.
²Medical Research Center for Combinatorial Tumor Immunotherapy, Chonnam National University Medical School, Gwangju, Republic of Korea.
³Department of Thoracic and Cardiovascular Surgery, Chonnam National University Medical School, Hwasun Hospital, Gwangju, Republic of Korea.
⁴National Immunotherapy Innovation Center, Chonnam National University Medical School, Gwangju, Republic of Korea.
⁵BioMedical Sciences Graduate Program, Chonnam National University Medical School, Gwangju, Republic of Korea.
⁶Selecxine Inc., Seoul, Republic of Korea.
⁷Department of Internal Medicine, Chonnam National University Medical School, Hwasun Hospital, Gwangju, Republic of Korea.
⁸These authors contributed equally: Sung-Woo Lee, Ju Sik Yun.

^*Corresponding authors: correspondence to In-Jae Oh or Jae-Ho Cho

Abstract

Suppression of tumor-reactive CD8⁺ T cells is common within the tumor microenvironment. However, little is known about how tumors systemically affect the overall CD8⁺ T cell compartment. Here we demonstrate that peripheral blood CD8⁺ T cells from patients with lung cancer showed altered compositions particularly within CD45RA^-CCR7^- effector memory subpopulation. Specifically, patients with lung cancer exhibited increased frequency of more differentiated effector memory cells, which are less susceptible to T cell-receptor-induced proliferation. Further analysis using single-cell RNA sequencing revealed that these alterations were correlated with reduced quiescence and increased spontaneous activation at a systemic level, indicative of homeostatic dysregulation of the entire CD8⁺ T cell population. This phenomenon was found to be correlated with a poor clinical response to immune checkpoint inhibitor therapy across four independent cohorts, consisting of a total of 224 patients with lung cancer. These findings suggest that lung cancers continue to counteract potentially tumor-reactive CD8⁺ T cells by inducing homeostatic dysregulation of the entire CD8⁺ T cell compartment systematically.

논문정보

형식Research article
게재일2025년 05월 (BRIC 등록일 2025-05-02)
연구진국내 연구진
분야 의약학 > 면역의학

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