期刊
JOURNAL FOR IMMUNOTHERAPY OF CANCER
卷 9, 期 6, 页码 -出版社
BMJ PUBLISHING GROUP
DOI: 10.1136/jitc-2021-002588
关键词
adaptive immunity; antibody formation; autoimmunity; CD4-Positive T-Lymphocytes; costimulatory and Inhibitory T-Cell receptors
资金
- Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [BA 5132/1-2 (252623821)]
- Germany's Excellence Strategy EXC2151 [390873048]
Cancer immunotherapy using immune checkpoint inhibitors has revolutionized the treatment of various cancers, but the precise etiology of immune-related adverse events (irAEs) observed as side effects is not fully understood. The function of T follicular helper (Tfh) cells in patients receiving ICIs is critically impacted, potentially providing a link between ICI treatment and the development of secondary autoimmunity.
Cancer immunotherapy utilizing immune checkpoint inhibitors (ICIs) has revolutionized the treatment of numerous cancer types. As the underlying mechanism of these treatments lies in the interference with inhibitory signals that usually impair potent antitumor immunity, for example, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and the programmed cell death protein 1 (PD-1):programmed death-ligand 1/2 (PD-L1/2) pathway, it is not surprising that this could also promote exaggerated adaptive immune responses to unrelated antigen specificities. One of the side effects of ICI-based cancer immunotherapy that is increasingly observed in the clinic is immune-related adverse events (irAEs), including various types of autoimmunity. However, the precise etiology is incompletely understood. T follicular helper (Tfh) cells provide essential help to B cells for potent antibody responses and their tumor tissue presence is often correlated with a better outcome in several solid tumor entities. Importantly, these CD4(+) T cells express very high amounts of PD-1 and other co-stimulatory and inhibitory receptors. Here, we address the hypothesis that targeting CTLA-4 or PD-1 and its ligand PD-L1 critically impacts the function of Tfh cells in patients that receive these ICIs, thereby providing a link between ICI treatment and the development of secondary autoimmunity.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据