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Updated: Jun 28, 2025
Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells
Published on: March 7, 2025
B cells and the coordination of immune checkpoint inhibitor response in patients with solid tumors
Ronan Flippot1,2, Marcus Teixeira3,2, Macarena Rey-Cardenas3,2
1Department of Medical Oncology, Gustave Roussy, Université Paris Saclay, Villejuif, France RONAN.FLIPPOT@gustaveroussy.fr.
Abstract:
Immunotherapy profoundly changed the landscape of cancer therapy by providing long-lasting responses in subsets of patients and is now the standard of care in several solid tumor types. However, immunotherapy activity beyond conventional immune checkpoint inhibition is plateauing, and biomarkers are overall lacking to guide treatment selection. Most studies have focused on T cell engagement and response, but there is a growing evidence that B cells may be key players in the establishment of an organized immune response, notably through tertiary lymphoid structures. Mechanisms of B cell response include antibody-dependent cellular cytotoxicity and phagocytosis, promotion of CD4+ and CD8+ T cell activation, maintenance of antitumor immune memory. In several solid tumor types, higher levels of B cells, specific B cell subpopulations, or the presence of tertiary lymphoid structures have been associated with improved outcomes on immune checkpoint inhibitors. The fate of B cell subpopulations may be widely influenced by the cytokine milieu, with versatile roles for B-specific cytokines B cell activating factor and B cell attracting chemokine-1/CXCL13, and a master regulatory role for IL-10. Roles of B cell-specific immune checkpoints such as TIM-1 are emerging and could represent potential therapeutic targets. Overall, the expanding field of B cells in solid tumors of holds promise for the improvement of current immunotherapy strategies and patient selection.
Insights
B cells, often overlooked in cancer, are emerging as key players in immunotherapy. Their presence and specific roles, like forming tertiary lymphoid structures, correlate with better patient outcomes in solid tumors.
Area of Science:
- Immunology
- Oncology
- Cancer Therapy
Background:
- Immunotherapy has revolutionized cancer treatment, offering durable responses but facing plateauing efficacy and a lack of predictive biomarkers.
- Current research predominantly focuses on T cell responses, yet B cells are increasingly recognized for their significant role in anti-tumor immunity.
Purpose of the Study:
- To explore the multifaceted roles of B cells in solid tumor immunity.
- To highlight B cell involvement in tertiary lymphoid structures and their impact on immunotherapy outcomes.
- To identify potential B cell-related biomarkers and therapeutic targets for enhancing cancer immunotherapy.
Main Methods:
- Review of existing literature on B cell functions in solid tumors and their interaction with immunotherapy.
- Analysis of associations between B cell populations, tertiary lymphoid structures, and patient responses to immune checkpoint inhibitors.
- Investigation of cytokine influences (e.g., IL-10, BAFF, CXCL13) and B cell-specific checkpoints (e.g., TIM-1) in the tumor microenvironment.
Main Results:
- B cells contribute to anti-tumor responses through mechanisms like antibody-dependent cellular cytotoxicity and promotion of T cell activation.
- The presence of tertiary lymphoid structures, often B cell-rich, is linked to improved outcomes with immune checkpoint inhibitors in various solid tumors.
- Cytokines and B cell-specific checkpoints are identified as crucial regulators of B cell function in the tumor milieu.
Conclusions:
- B cells are critical components of the anti-tumor immune response and hold significant promise for improving immunotherapy efficacy.
- B cell dynamics and biomarkers, including tertiary lymphoid structures and specific subpopulations, could enhance patient selection for immunotherapy.
- Targeting B cell-specific pathways presents a potential new avenue for developing novel cancer immunotherapies.
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