Deeley Research Centre, BC Cancer, Victoria, British Columbia, Canada.
Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
Nat Rev Cancer. 2022 Jul;22(7):414-430. doi: 10.1038/s41568-022-00466-1. Epub 2022 Apr 7.
Although immunotherapy research to date has focused largely on T cells, there is mounting evidence that tumour-infiltrating B cells and plasma cells (collectively referred to as tumour-infiltrating B lymphocytes (TIL-Bs)) have a crucial, synergistic role in tumour control. In many cancers, TIL-Bs have demonstrated strong predictive and prognostic significance in the context of both standard treatments and immune checkpoint blockade, offering the prospect of new therapeutic opportunities that leverage their unique immunological properties. Drawing insights from autoimmunity, we review the molecular phenotypes, architectural contexts, antigen specificities, effector mechanisms and regulatory pathways relevant to TIL-Bs in human cancer. Although the field is young, the emerging picture is that TIL-Bs promote antitumour immunity through their unique mode of antigen presentation to T cells; their role in assembling and perpetuating immunologically 'hot' tumour microenvironments involving T cells, myeloid cells and natural killer cells; and their potential to combat immune editing and tumour heterogeneity through the easing of self-tolerance mechanisms. We end by discussing the most promising approaches to enhance TIL-B responses in concert with other immune cell subsets to extend the reach, potency and durability of cancer immunotherapy.
虽然迄今为止的免疫疗法研究主要集中在 T 细胞上，但越来越多的证据表明，肿瘤浸润 B 细胞和浆细胞（统称为肿瘤浸润 B 淋巴细胞（TIL-B））在肿瘤控制中具有关键的协同作用。在许多癌症中，TIL-B 在标准治疗和免疫检查点阻断的背景下具有强烈的预测和预后意义，为利用其独特的免疫学特性提供了新的治疗机会。我们从自身免疫中汲取灵感，回顾了与人类癌症中的 TIL-B 相关的分子表型、结构背景、抗原特异性、效应机制和调节途径。尽管该领域还很年轻，但新出现的情况表明，TIL-B 通过其独特的向 T 细胞呈递抗原的方式促进抗肿瘤免疫；它们在组装和维持涉及 T 细胞、髓样细胞和自然杀伤细胞的免疫“热”肿瘤微环境中的作用；以及通过缓解自身耐受机制来对抗免疫编辑和肿瘤异质性的潜力。最后，我们讨论了最有前途的方法来增强 TIL-B 与其他免疫细胞亚群的反应，以扩大癌症免疫治疗的范围、效力和持久性。
