Journal of translational medicine · 2026
Circulating CD28-KLRG1+CD8+ T cells involve in systemic and local immunity that predicts chemoimmunotherapy outcomes in advanced NSCLC.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Zhou Jian, Bie Hongyu, You Yi, Li Jiarui, Liu Jiawei, Li Shijia, Huang Hui, Zhou Li, Hui Zhenzhen, Zhang Wencheng, Meng Yiran, Lin Hai, Zheng Liuqing, Qi Ying, Ji Zhenyu, Yu Wenwen, Wang Meng, Ren Xiubao, Yan Cihui
Аннотация
BACKGROUND: Chemoimmunotherapy has become the standard first-line treatment for advanced non-small cell lung cancer (NSCLC). Deciphering the T-cell subset responsible for chemoimmunotherapy and easily tested conveniently is critical in predicting the treatment outcomes.
METHODS: Based on peripheral blood collected from patients enrolled from a phase 2 clinical study (ClinicalTrials.gov NCT04836728), we performed multi-color flow cytometry and unsupervised analysis to explore correlations with therapeutic outcomes. We integrated single-cell RNA and T-cell receptor (TCR) sequencing in 36 samples, including peripheral blood, tumors and non-tumor tissues, from 8 NSCLC patients to interpret the correlation, which was further verified using blood samples, orthotopic and subcutaneous lung cancer mouse model.
RESULTS: The baseline CD28-KLRG1+CD57+ and on-treatment CD28-KLRG1+ CD8+ T cells in peripheral blood were independent factors which indicated improved treatment outcomes in advanced NSCLC patients receiving first-line chemoimmunotherapy. While being in a late-differentiated T-cell status, these cells were clonally expanded and reinvigorated during chemoimmunotherapy, serving as a peripheral T-cell pool for supplying potential tumor-reactive T cells in tumors, and reversely differentiating into less-differentiated subsets. The zinc-metallothionein pathway regulated the CD28-KLRG1+ CD8+ T-cell subset. Zinc supplementation combined with chemoimmunotherapy improved both local and systemic antitumor immune responses in mouse model.
CONCLUSIONS: Circulating CD28-KLRG1+ CD8+ T cells are valuable and convenient biomarkers for first-line chemoimmunotherapy in advanced NSCLC and provide insight into how late-differentiated or senescent T cells engage in the antitumor immunity when immunotherapy is added to conventional therapies.
METHODS: Based on peripheral blood collected from patients enrolled from a phase 2 clinical study (ClinicalTrials.gov NCT04836728), we performed multi-color flow cytometry and unsupervised analysis to explore correlations with therapeutic outcomes. We integrated single-cell RNA and T-cell receptor (TCR) sequencing in 36 samples, including peripheral blood, tumors and non-tumor tissues, from 8 NSCLC patients to interpret the correlation, which was further verified using blood samples, orthotopic and subcutaneous lung cancer mouse model.
RESULTS: The baseline CD28-KLRG1+CD57+ and on-treatment CD28-KLRG1+ CD8+ T cells in peripheral blood were independent factors which indicated improved treatment outcomes in advanced NSCLC patients receiving first-line chemoimmunotherapy. While being in a late-differentiated T-cell status, these cells were clonally expanded and reinvigorated during chemoimmunotherapy, serving as a peripheral T-cell pool for supplying potential tumor-reactive T cells in tumors, and reversely differentiating into less-differentiated subsets. The zinc-metallothionein pathway regulated the CD28-KLRG1+ CD8+ T-cell subset. Zinc supplementation combined with chemoimmunotherapy improved both local and systemic antitumor immune responses in mouse model.
CONCLUSIONS: Circulating CD28-KLRG1+ CD8+ T cells are valuable and convenient biomarkers for first-line chemoimmunotherapy in advanced NSCLC and provide insight into how late-differentiated or senescent T cells engage in the antitumor immunity when immunotherapy is added to conventional therapies.