B cells and the therapeutic index of checkpoint blockade.
- 1Chinese Institute for Molecular and Cellular Therapeutics, Chinese Institutes for Medical Research, Beijing, China.
- 2School of Basic Medical Sciences, Capital Medical University, Beijing, China.
Abstract
Combined CTLA-4 and PD-1 blockade is effective in treating melanoma and additional cancers but frequently causes immune-related adverse events (irAEs). irAEs cause treatment disruption and discontinuation and remain difficult to manage clinically. In this issue, Dhodapkar and colleagues assessed data from a small randomized clinical trial testing rituximab-mediated B cell depletion in combined CTLA-4/PD-1 blockade-treated patients with advanced melanoma. Despite premature discontinuation of the trial due to a high rate of rituximab hypersensitivity, they report that preemptive B cell depletion was associated with fewer severe toxicities without evident loss of antitumor activity. These findings raise broader questions about the organization of checkpoint-induced autoimmunity, the emerging concept of immune reset, and the compartment-specific roles of B cells in antitumor immunity.
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BibTeX
@article{li2026cells,
title = {{B cells and the therapeutic index of checkpoint blockade.}},
author = {Chuan-Yuan Li},
journal = {The Journal of clinical investigation},
year = {2026},
month = nov,
doi = {10.1172/jci212237},
url = {https://europepmc.org/article/MED/42969237},
note = {CC BY},
}
RIS
TY - JOUR
TI - B cells and the therapeutic index of checkpoint blockade.
AU - Chuan-Yuan Li
PY - 2026
DA - 2026/11/02
JO - The Journal of clinical investigation
DO - 10.1172/jci212237
UR - https://europepmc.org/article/MED/42969237
AB - Combined CTLA-4 and PD-1 blockade is effective in treating melanoma and additional cancers but frequently causes immune-related adverse events (irAEs). irAEs cause treatment disruption and discontinuation and remain difficult to manage clinically. In this issue, Dhodapkar and colleagues assessed data from a small randomized clinical trial testing rituximab-mediated B cell depletion in combined CTLA-4/PD-1 blockade-treated patients with advanced melanoma. Despite premature discontinuation of the trial due to a high rate of rituximab hypersensitivity, they report that preemptive B cell depletion was associated with fewer severe toxicities without evident loss of antitumor activity. These findings raise broader questions about the organization of checkpoint-induced autoimmunity, the emerging concept of immune reset, and the compartment-specific roles of B cells in antitumor immunity.
SN - 0021-9738
SN - 1558-8238
ER -