1)三峡大学基础医学院,宜昌 443000;2)三峡大学肿瘤微环境与免疫治疗湖北省重点实验室,宜昌 443000
湖北省自然科学基金(2022CFB320),宜昌市医疗卫生科技项目(A23-1-072)和肿瘤微环境与免疫治疗湖北省重点实验室开放基金(2023KZL019)资助。
1)School of Basic Medicine, China Three Gorges University, Yichang 443000, China;2)Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang 443000, China
This work was supported by grants from Hubei Provincial Natural Science Foundation (2022CFB320),Yichang Medical and Health Technology Project (A23-1-072), and Hubei Provincial Key Laboratory of Tumor Microenvironment and Immunotherapy Open Fund (2023KZL019).
近年来,肿瘤浸润性B淋巴细胞(tumor-infiltrating B lymphocytes,TIL-B)在肿瘤的发生和发展中扮演着复杂且重要的角色。这些细胞通过多种机制参与抗肿瘤免疫反应,但同时也可能在特定刺激下获得抑制功能,转化为调节性B细胞(regulatory B cells,Bregs),进而抑制肿瘤免疫应答,促进肿瘤的进展。越来越多的证据表明,TIL-B不仅是抗肿瘤免疫治疗中有效的靶标,而且在疾病预后方面也具有重要作用。本文综述了TIL-B研究现状,总结了其在肿瘤免疫中的作用机制,分析了当前的治疗策略和预后评估方法,并对未来的研究方向进行了展望。通过深入理解TIL-B的复杂性,可以为开发新的肿瘤治疗策略提供理论基础和潜在靶点。
In recent years, tumor-infiltrating B lymphocytes (TIL-B) play a complex and important role in tumorigenesis and tumor development. TIL-B contains various subpopulations, which can be broadly classified into subpopulations of tumor-suppressing B cells, such as antigen-presenting B cells and plasma cells; and subpopulations of tumor-promoting B cells, such as regulatory B cells (Bregs). The anti-tumor mechanisms of TIL-B contain many aspects, including the secretion of specific antibodies such as IgG and IgA; activation of T cells through antigen presentation; release of cytokines that affect tumor cell growth; direct killing of target cells through the Fas/FasL and perforin pathways; and enhancement of anti-tumor immunity through interactions with T cells. The pro-tumor mechanism of TIL-B also includes many aspects, such as Bregs can inhibit anti-tumor immunity by secreting cytokines, inducing the production of regulatory T cells (Tregs), and inhibiting the interaction between T cells and antigen presenting cells (APCs). Atypical memory (AtM) B cells and leucine-tRNA-synthase-2 (LARS2) -expressing B cells (LARS B) can also promote tumor progression by secreting cytokines such as TNF-α and TGF-β. Based on the above mechanisms, a variety of tumor therapies are now available. Firstly, the anti-tumor effect of TIL-B can be enhanced. Immune checkpoint blockade therapy is a classical immunotherapy method, and TIM-1 is a key checkpoint and has achieved certain efficacy. In addition, the development of suitable novel antibodies, safe and effective TIL-B vaccines are also promising therapeutic methods. Adoptive metastatic B-cell therapy, direct activation of B-cells, chemotherapy and targeted drugs is limited because of the high technical requirements, high toxicity and uncertainty of efficacy. In the future, it is expected that further research will gradually expand the scope of its application to achieve more effective treatment for tumor patients. Selective depletion of B cells is an immunotherapy based on the inhibition of Bregs subpopulations to achieve anti-tumor effects. The next step is to develop more efficacious targeted drugs by understanding the phenotypic and functional differences of Bregs. Finally, TIL-B can be involved in the treatment and prognosis of tumors as a predictive tumor immune marker. The efficacy of treatment can be simply assessed by observing TIL-B distribution and density in tumor. Stress-responsive memory B cells and tumor-associated atypical B cells (TAAB) have clearly shown to be associated with shorter and longer survival in cancer patients, thus being used as biomarkers of immunotherapeutic response in human cancers. This paper reviews the current status of TIL-B research, summarizes its mechanism of action in tumor immunity, analyses current therapeutic strategies and prognostic assessment methods. Future focus on understanding the functional heterogeneity and molecular regulatory mechanisms of TIL-B is essential for optimising tumor immunotherapy strategies. The systematic study of TIL-B characteristics and mechanisms of action in different tumor types can help provide a theoretical basis and potential targets for the development of new tumor therapeutic strategies.
黄茗,陈锦秀,张雨乐,董想,曹春雨,吴红艳.肿瘤浸润性B淋巴细胞在肿瘤免疫中的作用及临床应用前景[J].生物化学与生物物理进展,2025,52(3):615-625
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