生物
T细胞
CD8型
淋巴瘤
免疫系统
细胞毒性T细胞
间变性大细胞淋巴瘤
免疫学
癌症研究
遗传学
体外
作者
Xiufen Chen,Jovian Yu,Girish Venkataraman,Sonali M. Smith,Meng-Jie Chen,Alan Cooper,Sravya Tumuluru,Joshua Brody,James Godfrey,Justin Kline
出处
期刊:Cancer immunology research
[American Association for Cancer Research]
日期:2024-01-19
标识
DOI:10.1158/2326-6066.cir-23-0547
摘要
Abstract The classical Hodgkin lymphoma (cHL) environment is comprised of a dense and complex immune cell infiltrate interspersed with rare malignant Hodgkin-Reed-Sternberg (HRS) cells. HRS cells are actively surveilled by endogenous T cells, but data linking phenotypic and functional T cell states with clonality at the single cell level in cHL is lacking. To address this knowledge gap, we performed paired single cell RNA and T cell receptor sequencing on 14 cHL and 5 reactive lymphoid tissue specimens. Conventional CD4+ T cells dominated the cHL landscape. However, recurrent clonal expansion within effector and exhausted CD8+ T cell and regulatory T cell clusters was uniquely observed in cHL specimens. Multi-plex flow cytometric analysis revealed that most lymphoma-resident T cells produced effector cytokines upon ex vivo restimulation, arguing against a profound dysfunctional T cell state in cHL. Our results raise new questions about the nature of T cells that mediate the anti-lymphoma response following PD-1 blockade therapy in cHL.
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