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B lymphocyte inhibition of anti-tumor response depends on expansion of Treg but is independent of B-cell IL-10 secretion

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Abstract

The mechanisms by which B lymphocytes inhibit anti-tumor immunity remain poorly understood. Murine EMT-6 mammary tumors grow readily in immune competent mice (BALB/c), but poorly in B-cell-deficient μ−/− BALB/c mice (BCDM). T regulatory cell (Treg) expansion and function were impaired in BCDM compared with BALB/c. In this study, we compared tumor growth, Treg cell proliferation, tumor lymphocyte infiltration and cytolytic T cell activity in BALB/c, BCDM and BCDM partially reconstituted with B cells by adoptive transfer (BCDM+B). Partial reconstitution of BCDM with adoptively transferred B cells restored EMT-6 tumor growth, which was independent of IL-10 secretion by B cells. Instead, high frequencies of intratumoral B cells were associated with increased recruitment and proliferation of Treg cells within the tumor microenvironment. The B-cell-dependent accumulation of Treg within the tumor microenvironment was associated with reduced tumor infiltration by CD49+ NK and CD8+ T cells and reduced cytotoxic T cell activity against EMT-6 targets. Our studies indicate that tumor-dependent immunosuppression of T-cell-mediated anti-tumor immunity is coordinated within the tumor microenvironment by B-cell-dependent cross talk with Treg cells, which does not require production of IL-10 by B cells.

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Acknowledgments

We are grateful to Dr. Dietlinde Wolf for kindly providing the PC61 antibody and the staff of the SCCC flow laboratory for excellent technical support. This work was financially supported by National Institution of Health (Grant 5-P01-CA-109094-04) and the Arnall Family Foundation.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

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

    Yu Zhang, Yair Eliav, Seung-uon Shin & Joseph D. Rosenblatt

  2. Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, 33136, USA

    Taylor H. Schreiber & Eckhard R. Podack

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

    Tamar Tadmor

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  1. Yu Zhang
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  2. Yair Eliav
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  7. Joseph D. Rosenblatt
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Correspondence to Joseph D. Rosenblatt.

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Zhang, Y., Eliav, Y., Shin, Su. et al. B lymphocyte inhibition of anti-tumor response depends on expansion of Treg but is independent of B-cell IL-10 secretion. Cancer Immunol Immunother 62, 87–99 (2013). https://doi.org/10.1007/s00262-012-1313-6

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  • DOI: https://doi.org/10.1007/s00262-012-1313-6

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