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The absence of B lymphocytes reduces the number and function of T-regulatory cells and enhances the anti-tumor response in a murine tumor model

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Abstract

Increasing evidence suggests that B lymphocytes play a central role in inhibiting the immune response against certain tumors, but the underlying mechanisms by which B cells facilitate tumor growth are still poorly understood. In this study, we investigated how the presence or absence of B cells affects expansion and function of T-regulatory cells (‘T-regs’) in a murine breast tumor model (EMT-6). We compared tumor growth, and the number and function of T-reg cells in wild-type immune-competent mice (ICM) and B-cell-deficient mice (BCDM). Mice were either tumor-naive or implanted with EMT-6 mammary adenocarcinoma cells. Tumor growth was markedly inhibited in BCDM, compared to wild-type mice (ICM). Increased T-reg expansion as defined by CD4+/CD25+/FOXP3+ cells was evident following EMT-6 inoculation in ICM in comparison with non-tumor-bearing mice or compared to BCDM in which tumor had been implanted. The percentage and absolute number of T-regs in the spleen, tumor draining lymph nodes, and tumor bed were significantly reduced in BCDM compared to ICM. T-reg function, measured by suppression and proliferation assays, was also reduced in tumor inoculated BCDM compared to ICM. Our studies indicate that absence of B cells may play a role in augmenting the T-cell anti-tumor response, in part due to effects on T-regulatory cell expansion and function.

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Acknowledgments

This study was supported by NIH grant 5-P01-CA-109094-04 and the American Physician Fellowship (APF) for support of TT.

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Authors and Affiliations

  1. Haematology Unit, Bnai Zion Medical Center, Haifa, Israel

    Tamar Tadmor

  2. Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, USA

    Eckhard R. Podack & Joseph D. Rosenblatt

  3. Division of Hematology/Oncology, University of Miami Sylvester Comprehensive Cancer Center, 1475 NW 12th Avenue (D8-4), Suite 3300, Miami, FL, 33136, USA

    Yu Zhang, Hyun-Mi Cho & Joseph D. Rosenblatt

Authors
  1. Tamar Tadmor
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  2. Yu Zhang
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  3. Hyun-Mi Cho
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  4. Eckhard R. Podack
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  5. Joseph D. Rosenblatt
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Corresponding author

Correspondence to Joseph D. Rosenblatt.

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T. Tadmor and Y. Zhang are contributed equally to this paper.

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Tadmor, T., Zhang, Y., Cho, HM. et al. The absence of B lymphocytes reduces the number and function of T-regulatory cells and enhances the anti-tumor response in a murine tumor model. Cancer Immunol Immunother 60, 609–619 (2011). https://doi.org/10.1007/s00262-011-0972-z

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  • DOI: https://doi.org/10.1007/s00262-011-0972-z

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