在免疫肿瘤学中，传统上关注的焦点是 αβ T 细胞，而主要针对这些淋巴细胞中的 PD-1 或​​ CTLA4 的免疫检查点抑制剂已经彻底改变了多种人类恶性肿瘤的治疗。然而，最近的研究强调了 B 细胞及其产生的抗体在对抗恶性进展中的关键作用，为免疫治疗提供了新的途径。我们的小组已经证明二聚体 IgA 可以穿透肿瘤细胞，中和内体中的致癌驱动因素，并将它们从细胞质中排出。这种机制见解表明，针对该途径的工程抗体可以有效地到达以前无法达到的目标。研究肿瘤内生发中心内的抗体产生并了解不同免疫球蛋白对恶性进展的影响可以为治疗手段提供新工具，包括开发肿瘤穿透抗体。本综述旨在阐明人类癌症中体液适应性免疫反应的本质，并探讨它们如何预示免疫治疗方式的新时代。通过扩大抗肿瘤免疫疗法的范围，这些方法有可能使更广泛的癌症患者受益，特别是通过利用肿瘤细胞穿透抗体。© 作者 2024。由牛津大学出版社代表出版白细胞生物学学会。版权所有。如需商业重复使用，请联系 reprints@oup.com 获取转载和转载的翻译权。所有其他权限都可以通过我们网站文章页面上的权限链接通过我们的 RightsLink 服务获得 - 如需了解更多信息，请联系journals.permissions@oup.com。

In immuno-oncology, the focus has traditionally been on αβ T cells, and immune checkpoint inhibitors that primarily target PD-1 or CTLA4 in these lymphocytes have revolutionized the management of multiple human malignancies. However, recent research highlights the crucial role of B cells and the antibodies they produce in antagonizing malignant progression, offering new avenues for immunotherapy. Our group has demonstrated that dimeric IgA can penetrate tumor cells, neutralize oncogenic drivers in endosomes, and expel them from the cytosol. This mechanistic insight suggests that engineered antibodies targeting this pathway may effectively reach previously inaccessible targets. Investigating antibody production within intratumoral germinal centers and understanding the impact of different immunoglobulins on malignant progression could furnish new tools for the therapeutic arsenal, including the development of tumor-penetrating antibodies. This review aims to elucidate the nature of humoral adaptive immune responses in human cancer and explore how they could herald a new era of immunotherapeutic modalities. By expanding the scope of anti-tumor immunotherapies, these approaches have the potential to benefit a broader range of cancer patients, particularly through the utilization of tumor cell-penetrating antibodies.© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.