Tumor-infiltrating plasma cell profiling after PD-1 blockade reveals tumor-specific antibodies
Year: 2026
Type: article
Abstract: The role of tumor-infiltrating B cells (TIL-Bs) in shaping anti-tumor responses in the context of immune checkpoint blockade remains incompletely understood. Here, we interrogate the humoral response in resected lung tumors from patients with non-small cell lung cancer (NSCLC) treated with neoadjuvant PD-1 blockade. We find that tumors orchestrate tertiary lymphoid structures with CD138 + plasma cells, from which we clone recombinant monoclonal antibodies (mAbs) using B cell receptors (BCRs) exhibiting somatic hypermutation and class switching. Several mAbs bind cell-surface citrullinated proteins, characteristic of cancer cells. Chimeric antigen receptor (CAR) T redirected with the soluble chain fragment variable (scFv) of our lead candidate antibody (PC-1) specifically target tumor cells and tumor-promoting myeloid cells in vivo without off-target activity. Moreover, ablation of the citrullination enzyme PADI2 in tumor-bearing mice eliminates reactivity to PC-1 and cytotoxic killing by the CAR. Our results implicate a therapeutic potential for tumor-infiltrating plasma cells that may be harnessed for cancer treatment.
Source: Cancer Cell
Authors: R. Ryan Meyerhoff, Alan Chen, Jenny O’Brien, Carmen M. Anadon, Luis Uriel Lopez Bailon, Dayan Carrion-Estrada, Koravit Poysungnoen, Jared Lindenberger, Gabor Kemeny, Liliana Lyniv, Vaibjav Jain, Ricardo Chaurio, Noah Plappert, Tyler Evangelous, Chan Soo Park, Alok Sinha, Eziafa Oduah, Carolyn Glass, Kent Weinhold, Simon Gregory, John W. Hickey, Priyamvada Acharya, Neal Ready, Jose R. Conejo-Garcia, Wilton B. Williams, Scott J. Antonia
Institutions: Duke University, Duke Medical Center
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $10,400
Awards: OR2H1 is an effective target for CAR T cells in human epithelial tumors, G3351748408, G5780585700, Leica Stellaris Confocal for a Campus-wide Shared Resource, Duke Radiation Oncology and Radiology Stimulating Access to Research in Residency, Crosstalk between butyrophilins and gamma delta T cells in human cancer, Novel immunotherapies using optimized tumor cell-penetrating antibodies, Inter-metastatic divergency in small cell lung cancer; implications for the design of future immunotherapies, Cancer Center Support Grant (CCSG)
OpenAlex ID: W7171401252