Leong Tracy L, Bryant Vanessa L
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Department of Respiratory and Sleep Medicine, Austin Health, Heidelberg, Victoria, Australia.
Transl Lung Cancer Res. 2021 Jun;10(6):2830-2841. doi: 10.21037/tlcr-20-788.
Metastatic lung cancer represents a significant global issue where it is responsible for the most cancer diagnoses and deaths worldwide. Treatment for advanced lung cancer has undergone a series of paradigm shifts from chemotherapy to targeted molecular agents to the most recent immunotherapy strategies. The most successful of the latter involves antibodies that block inhibitory receptors on tumor infiltrating T cells, thereby enhancing T cell activity against tumor cells. However, only a subset of patients demonstrate durable responses to these drugs and treatment resistance is common. Emerging evidence suggests that a critical role exists for B cells as more than a bystander immune cell in the tumor microenvironment (TME). However, this role is likely context-specific where B cells comprise distinct subtypes with unique effector functions that may result in anti- or pro-tumor effects. As such, the balance between various B cell subtypes affects the net B cell impact upon tumor immunity. To date, the factors needed to polarize B cell function toward anti-tumor activity are unclear. Understanding B cell biology in the lung cancer setting will help redefine and refine treatment strategies to augment anti-tumor immunity. This article presents a review of the literature describing the current knowledge of the development and function of B cells, and explores their role in lung cancer and potential as an immunotherapeutic strategy and as a predictive marker for response to immune checkpoint blockade.
转移性肺癌是一个重大的全球性问题，在全球范围内，它导致了最多的癌症诊断病例和死亡。晚期肺癌的治疗已经经历了一系列的范式转变，从化疗到靶向分子药物，再到最新的免疫治疗策略。后者中最成功的策略涉及阻断肿瘤浸润T细胞上抑制性受体的抗体，从而增强T细胞对肿瘤细胞的活性。然而，只有一部分患者对这些药物表现出持久的反应，治疗耐药很常见。新出现的证据表明，B细胞在肿瘤微环境（TME）中不仅仅是旁观者免疫细胞，还发挥着关键作用。然而，这种作用可能因具体情况而异，因为B细胞包含具有独特效应功能的不同亚型，这些功能可能导致抗肿瘤或促肿瘤作用。因此，各种B细胞亚型之间的平衡会影响B细胞对肿瘤免疫的总体影响。迄今为止，使B细胞功能向抗肿瘤活性极化所需的因素尚不清楚。了解肺癌环境中的B细胞生物学将有助于重新定义和完善治疗策略，以增强抗肿瘤免疫力。本文对描述B细胞发育和功能的现有知识的文献进行了综述，并探讨了它们在肺癌中的作用以及作为免疫治疗策略和免疫检查点阻断反应预测标志物的潜力。
