Abstract
The role of B cells in the anti-tumor immune response remains controversial. An increase in the number of B cells in the peripheral blood of some tumor patients has been associated with poor immunotherapy efficacy. However, the mechanism leading to the generation of these cells is not well-described. Using a fibrosarcoma model, we show that intraperitoneal administration of a xenogeneic antigen in tumor-bearing mice evokes large increases in antigen-specific serum immunoglobulin formation compared to tumor-naïve mice. An inability of tumor-bearing mice to induce enhanced antibody production after myeloid cell depletion suggests the antibody responses are CD11b+ myeloid cell-dependent. In vitro, CD11b+ myeloid cells promoted B cell proliferation, activation, and survival. High levels of tumor necrosis factor (TNF)-α were produced by CD11b+ cells, and TNF-α blockade inhibited B cell responses. CD11b+ cells appear to be important promoters of B cell responses and targeting B cells may increase the efficacy of immunotherapy in tumor-bearing hosts.
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Funding
This work was supported by the National Natural Science Foundation of China (Grant No. 81972690 and 81000914) and Medical Science and Technology Research Project of Health Commission of Henan Province (2018010033). The funding bodies played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.
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ZW designed and performed experiments, analyzed data, and wrote the manuscript. YL, LP, BT, SY, XY, QF analyzed data and edited the manuscript. LC performed experiments. YL is responsible for bioinformatics analysis. ZQ supervised the study.
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Wang, Z., Liu, Y., Peng, L. et al. Role of fibrosarcoma-induced CD11b+ myeloid cells and tumor necrosis factor-α in B cell responses. Oncogene 41, 1434–1444 (2022). https://doi.org/10.1038/s41388-022-02187-z
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DOI: https://doi.org/10.1038/s41388-022-02187-z