准确翻译:肿瘤内T细胞和B细胞受体结构与免疫抗PD-1/L1治疗的独特免疫肿瘤微环境特征和临床疗效相关。
Intratumoral T-cell and B-cell receptor architecture associates with distinct immune tumor microenvironment features and clinical outcomes of anti-PD-1/L1 immunotherapy.
发表日期:2023 Aug
作者:
Aimilia Schina, Zsofia Sztupinszki, Inge Marie Svane, Zoltan Szallasi, Göran Jönsson, Marco Donia
来源:
Journal for ImmunoTherapy of Cancer
摘要:
肿瘤微环境中B细胞和T细胞之间有效的合作可能导致已建立的肿瘤的退缩。B细胞和T细胞可以通过它们的受体复合物以极高的特异性识别肿瘤抗原。然而,是否一种多样的肿瘤细胞内B细胞和T细胞受体(BCR,TCR)亚基组合对肿瘤免疫微环境(TIME)和接受免疫治疗患者的临床结果产生影响尚不清楚。我们从大型临床数据集中提取了关于BCR和TCR亚基组合多样性的信息,并测量了免疫受体多样性特征、TIME和接受抗PD-1/PD-L1免疫治疗患者的临床结果之间的关联。在多种肿瘤类型中,TCR亚基组合的多样性与高度活化的TIME强相关,而BCR多样性更与抗体反应相关,但与整体B细胞浸润以及与肿瘤内CD8+T细胞活性相关的测量值无关。无论是TCR还是BCR多样性都不是多种癌症类型患者存活的独立预测生物标志物。然而,TCR和BCR多样性与已建立的免疫治疗反应生物标志物结合后,可以显著改善预测模型的性能。总的来说,这些数据表明肿瘤内与BCR多样性和抗体反应相关的B细胞存在一种尚未探索的免疫学作用,而此作用与经典的抗癌T细胞肿瘤内活动是独立的。
© 作者(或他们的雇主)2023。在CC BY-NC下允许再使用。不可商业再利用。有关权利和权限,请参阅BMJ的发布说明。
Effective cooperation between B-cells and T-cells within the tumor microenvironment may lead to the regression of established tumors. B-cells and T-cells can recognize tumor antigens with exquisite specificity via their receptor complexes. Nevertheless, whether a diverse intratumoral B-cells and T-cell receptor (BCR, TCR) repertoire affects the tumor immune microenvironment (TIME) and clinical outcomes in patients treated with immunotherapy is unclear.We extracted information on BCR and TCR repertoire diversity from large clinical datasets and measured the association between immune receptor diversity features, the TIME, and clinical outcomes of patients treated with anti-PD-1/PD-L1 immunotherapy.In multiple tumor types, an increasingly diverse TCR repertoire was strongly associated with a highly activated TIME, while BCR diversity was more associated with antibody responses but not with the overall B-cell infiltration nor with measures related to intratumoral CD8+T cell activity. Neither TCR nor BCR diversity was independent prognostic biomarkers of survival across multiple cancer types. However, both TCR and BCR diversity improved the performance of predictive models combined with established biomarkers of response to immunotherapy.Overall, these data indicate a currently unexplored immunological role of intratumoral B-cells associated with BCR diversity and antibody responses but independent of classical anticancer T-cells intratumoral activities.© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.