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Role of B cells in intratumoral MBTA immunotherapy of murine pheochromocytoma model

O. Uher, K. Hadrava Vanova, K. Petrlakova, R. Labitt, R. Lencova, A. Frejlachova, J. Ye, H. Wang, M. Masarik, J. Zenka, Z. Zhuang, K. Pacak

. 2025 ; 39 (1) : 101941. [pub] 20240911

Language English Country Netherlands

Document type Journal Article, Review, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Intramural

Grant support
Z01 HD008735 Intramural NIH HHS - United States
ZIA HD008735 Intramural NIH HHS - United States

Immunotherapy represents a revolutionary advancement in cancer treatment, which has traditionally focused on T cells; however, the role of B cells in cancer immunotherapy has gained interest because of their role in antigen presentation, antibody production, and cytokine release. In this study, we examined the role of B cells in previously developed intratumoral MBTA therapy (mannan-BAM, TLR ligands, and anti-CD40 antibody) in murine models of MTT pheochromocytoma. The results indicated that B cells significantly enhance the success of MBTA therapy, with wild-type mice exhibiting a lower tumor incidence and smaller tumors compared with B cell-deficient mice. Increased IL-6 and TNF-alpha levels indicated severe inflammation and a potential cytokine storm in B cell-deficient mice. Neutralization of TNF-alpha ameliorated these complications but resulted in increased tumor recurrence. The results highlight the important role of B cells in enhancing the immune response and maintaining immune homeostasis during MBTA therapy. Our findings offer new insights into improving therapeutic outcomes.

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$a Immunotherapy represents a revolutionary advancement in cancer treatment, which has traditionally focused on T cells; however, the role of B cells in cancer immunotherapy has gained interest because of their role in antigen presentation, antibody production, and cytokine release. In this study, we examined the role of B cells in previously developed intratumoral MBTA therapy (mannan-BAM, TLR ligands, and anti-CD40 antibody) in murine models of MTT pheochromocytoma. The results indicated that B cells significantly enhance the success of MBTA therapy, with wild-type mice exhibiting a lower tumor incidence and smaller tumors compared with B cell-deficient mice. Increased IL-6 and TNF-alpha levels indicated severe inflammation and a potential cytokine storm in B cell-deficient mice. Neutralization of TNF-alpha ameliorated these complications but resulted in increased tumor recurrence. The results highlight the important role of B cells in enhancing the immune response and maintaining immune homeostasis during MBTA therapy. Our findings offer new insights into improving therapeutic outcomes.
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$a Hadrava Vanova, Katerina $u Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda 20892, MD, USA. Electronic address: katerina.hadravavanova@nih.gov
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$a Petrlakova, Katerina $u Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda 20892, MD, USA; Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Brno 62500 Czech Republic. Electronic address: katerina.petrlakova@med.muni.cz
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$a Labitt, Rachael $u Research Animal Management Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda 20892, MD, USA. Electronic address: rachael.labitt@nih.gov
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$a Lencova, Radka $u Department of Medical Biology, Faculty of Science, University of South Bohemia, Ceske Budejovice 37005, Czech Republic. Electronic address: lencor00@prf.jcu.cz
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$a Frejlachova, Andrea $u Department of Medical Biology, Faculty of Science, University of South Bohemia, Ceske Budejovice 37005, Czech Republic. Electronic address: frejla00@prf.jcu.cz
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$a Ye, Juan $u Neuro-Oncology Branch, National Cancer Institute, NIH, Bethesda 20892, MD, USA. Electronic address: juan.ye@nih.gov
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$a Wang, Herui $u Neuro-Oncology Branch, National Cancer Institute, NIH, Bethesda 20892, MD, USA. Electronic address: herui.wang@nih.gov
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$a Masarik, Michal $u Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Brno 62500 Czech Republic; Department of Physiology, Faculty of Medicine, Masaryk University, Brno 62500, Czech Republic; BIOCEV (Biotechnology and Biomedicine Center in Vestec), First Faculty of Medicine, Charles University, Vestec 25250, Czech Republic. Electronic address: masarik@med.muni.cz
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$a Zenka, Jan $u Department of Medical Biology, Faculty of Science, University of South Bohemia, Ceske Budejovice 37005, Czech Republic. Electronic address: jzenka@prf.jcu.cz
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$a Zhuang, Zhengping $u Neuro-Oncology Branch, National Cancer Institute, NIH, Bethesda 20892, MD, USA. Electronic address: zhengping.zhuang@nih.gov
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$a Pacak, Karel $u Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda 20892, MD, USA. Electronic address: karel@mail.nih.gov
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