肿瘤浸润B细胞:免疫机制、临床影响和治疗机会

Abstract 

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.

尽管迄今为止的免疫治疗研究主要集中在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抑制的背景下都显示出很强的预测和预后意义，提供了利用其独特的免疫特性的新治疗机会的前景。从自身免疫的角度出发，我们总结了与人类癌症中TIL- B相关的分子表型、结构背景、抗原特异性、效应机制和调控途径。

尽管这是一个新兴领域，但我们逐渐发现，TIL- B通过其独特的抗原呈递到T细胞的模式促进抗肿瘤免疫;它们在装配和维持免疫“热”肿瘤微环境，包括T细胞、髓细胞和自然杀伤细胞;它们具有通过放松自我耐受机制来对抗免疫编辑和肿瘤异质性的潜力。最后，我们讨论了最有希望的方法，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。