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

IF 6.1 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Best practice & research. Clinical endocrinology & metabolism Pub Date : 2024-09-11 DOI:10.1016/j.beem.2024.101941

Ondrej Uher, Katerina Hadrava Vanova, Katerina Petrlakova, Rachael Labitt, Radka Lencova, Andrea Frejlachova, Juan Ye, Herui Wang, Michal Masarik, Jan Zenka, Zhengping Zhuang, Karel Pacak

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引用次数: 0

Abstract

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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B 细胞在小鼠嗜铬细胞瘤模型瘤内 MBTA 免疫疗法中的作用

免疫疗法代表了癌症治疗的革命性进步，传统的癌症治疗主要集中在 T 细胞上；然而，由于 B 细胞在抗原呈递、抗体产生和细胞因子释放中的作用，它们在癌症免疫疗法中的作用也受到了关注。在本研究中，我们在 MTT 嗜铬细胞瘤小鼠模型中研究了 B 细胞在先前开发的瘤内 MBTA 疗法（甘露聚糖-BAM、TLR 配体和抗 CD40 抗体）中的作用。结果表明，B细胞能显著提高MBTA疗法的成功率，与B细胞缺陷小鼠相比，野生型小鼠的肿瘤发病率更低，肿瘤更小。IL-6和TNF-α水平升高表明B细胞缺陷小鼠存在严重的炎症和潜在的细胞因子风暴。中和 TNF-α 可改善这些并发症，但会导致肿瘤复发。这些结果突显了 B 细胞在 MBTA 治疗过程中增强免疫反应和维持免疫平衡的重要作用。我们的研究结果为改善治疗效果提供了新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Best practice & research. Clinical endocrinology & metabolism 医学-内分泌学与代谢

CiteScore

11.90

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Best Practice & Research Clinical Endocrinology & Metabolism is a serial publication that integrates the latest original research findings into evidence-based review articles. These articles aim to address key clinical issues related to diagnosis, treatment, and patient management. Each issue adopts a problem-oriented approach, focusing on key questions and clearly outlining what is known while identifying areas for future research. Practical management strategies are described to facilitate application to individual patients. The series targets physicians in practice or training.