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P96. Antigen-presenting B cells sustain checkpoint immunotherapy responses in liver cancer

Saturday, March 7, 2026
9:21 AM - 9:28 AM MST
Location: 105A-C
Introduction: The role of B cells in shaping immune checkpoint inhibitor (ICI) efficacy remains poorly defined in liver cancers. We combined prospective clinical trial data, single-cell analyses, and in vivo studies using the SB1 cholangiocarcinoma (CCA) mouse model to define mechanisms of B cell-driven antitumor immunity during checkpoint immunotherapy.


Methods: Prospective clinical data from a trial of anti-PD-L1, anti-CTLA-4, and anti-VEGF in patients with intrahepatic cholangiocarcinoma (iCCA) or hepatocellular carcinoma (HCC) were integrated with single-cell RNA sequencing (scRNA-seq) and histopathology. Complementary analyses with flow cytometry and adoptive transfer experiments were performed in the SB1 murine CCA model.


Results: Regimens including upfront anti-PD-L1 + anti-CTLA-4 double therapy and triple therapy with anti-VEGF showed superior PFS and OS compared to double therapy (6.8 vs 2.3 months; 14.5 vs 7.6 months). In the SB1 CCA mouse model, triple therapy promoted tertiary lymphoid structures. Knockout of activation induced cytidine deaminase (AICDA) delayed triple therapy efficacy, suggesting a potential role for B cell affinity maturation in early responses. AICDA knockouts also showed notable intratumoral infiltration of antigen-presenting (APC) B cells. In addition, adoptive transfer of ex vivo–expanded tumor-infiltrating B cells from either triple-therapy– or placebo (IgG)–treated SB1 CCA tumors appeared to delay tumor growth in recipient mice compared with those that did not receive B cell transfer. In patients, scRNA-seq revealed that plasma cells expanded in tumors after any ICI therapy compared with tumors from patients who underwent surgery alone, but these plasma cells exhibited exhaustion signatures.


Conclusions: Triple therapy efficacy appears to rely on B cell affinity maturation for early responses and may be sustained by infiltration of antigen-presenting B cells, suggesting antigen presentation, rather than plasma cell differentiation, could contribute to durable ICI benefit. Ongoing studies are validating these observations and further exploring the role of B cells in sustaining ICI efficacy.

Learning Objectives:

  • Interpret how B cell activity, including antigen presentation and affinity maturation, shapes responses to checkpoint immunotherapy in liver cancer.
  • Predict which B cell populations may indicate therapeutic benefit or resistance, informing patient selection and monitoring.
  • Integrate insights from human clinical and SB1 mouse model data to guide strategies combining surgery with immunotherapy.