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Role of fibrosarcoma-induced CD11b+ myeloid cells and tumor necrosis factor-α in B cell responses

Oncogene volume 41, pages 1434–1444 (2022)Cite this article

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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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Fig. 1: Patients with solid tumors who respond poorly to PD-1-based treatment have high levels of CD11b+CD33+HLA-DR− cells.
Fig. 2: Peripheral B cells were related to the efficacy of immunotherapy.
Fig. 3: CD11b+ cells promote naïve B cell activation, proliferation, and survival.
Fig. 4: TNF-α is involved in the interaction of CD11b+ cells and B cells.
Fig. 5: Increased humoral immune responses in tumor-bearing mice.
Fig. 6: CD11b+ cells play important roles in enhanced antibody formation in tumor-bearing mice.

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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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Authors and Affiliations

  1. Department of Immunotherapy, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China

    Zibing Wang & Shumin Yuan

  2. Department of Oncology, Third Affiliated Hospital of Xinxiang Medical College, Xinxiang, China

    Yuqing Liu

  3. Department of Respiratory Disease, Zhejiang Provincial People’s Hospital, Hangzhou, China

    Ling Peng

  4. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Brian Till

  5. Yangjiang Key Laboratory of Respiratory Diseases, Yangjiang People’s Hospital, Yangjiang, China

    Yuwei Liao

  6. Medical Oncology Department, Chinese PLA General Hospital, Beijing, China

    Xiang Yan

  7. GZMU-GIBH School of Life Sciences, Guangzhou Medical University, Guangzhou, China

    Lin Chen

  8. Department of General Surgery, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China

    Qiang Fu

  9. Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China

    Zhihai Qin

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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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Correspondence to Zibing Wang.

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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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