HIV 感染和 ART 暴露影响弥漫性大 B 细胞淋巴瘤的肿瘤 T 细胞受体库。
HIV infection and ART exposure impact tumor T-cell receptor repertoire of diffuse large B-cell lymphoma.
发表日期:2024 May 23
作者:
Sophia M Roush, Jenny Coelho, Alexander M Xu, Kaushik Puranam, Marriam Mponda, Edwards Kasonkanji, Maurice Mulenga, Tamiwe Tomoka, Jonathan Galeotti, Amy Brownlee, Hormas Ghadially, Maganizo Chagomerana, Blossom Damania, Matthew Painschab, Akil Merchant, Satish Gopal, Yuri Fedoriw
来源:
JCI Insight
摘要:
弥漫性大 B 细胞淋巴瘤 (DLBCL) 是全球最常见的淋巴瘤亚型,是 HIV 感染者 (HIV) 癌症死亡的主要原因。 HIV 感染和抗逆转录病毒治疗 (ART) 导致的 T 细胞区室重组可能对现代治疗选择产生影响,但目前对这些动态相互作用的理解有限。在这里,我们通过对一组 HIV 阴性 (HIV-)、经历过 HIV/ART 和从未接受过 HIV/ART 的 DLBCL 患者的 T 细胞受体 (TCR) 库进行测序,研究了 T 细胞对 DLBCL 的反应。与经历过 HIV 和 HIV/ART 的肿瘤 TCR 库相比,未经历过 HIV/ART 的肿瘤 TCR 库更具克隆性且彼此之间更加不同。此外,肿瘤和血液 TCR 库之间重叠的增加与生存率和 HIV/ART 状态的改善相关。我们的研究首次描述了非洲 DLBCL 队列中的 TCR 谱特征,并证明了 HIV 感染和 ART 暴露对 DLBCL TCR 谱的贡献。
The most common subtype of lymphoma globally, diffuse large B-cell lymphoma (DLBCL) is a leading cause of cancer death in people with HIV (HIV+). The restructuring of the T-cell compartment due to HIV infection and antiretroviral therapy (ART) may have implications for modern treatment selection, but current understanding of these dynamic interactions is limited. Here, we investigated the T-cell response to DLBCL by sequencing the T-cell receptor (TCR) repertoire in a cohort of HIV-negative (HIV-), HIV+/ART-experienced and HIV+/ART-naïve DLBCL patients. HIV+/ART-naïve tumor TCR repertoires were more clonal and more distinct from each other than HIV- and HIV+/ART-experienced. Further, increased overlap between tumor and blood TCR repertoires was associated with improved survival and HIV/ART status. Our study describes TCR repertoire characteristics for the first time in an African DLBCL cohort and demonstrates contributions of HIV infection and ART exposure to the DLBCL TCR repertoire.