B cell regulation of anti-tumor immune response

Yu Zhang, Richard Morgan, Eckhard R. Podack, Joseph D Rosenblatt

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Our laboratory has been investigating the role of B cells on tumor immunity. We have studied the immune response in mice that are genetically lacking in B cells (BCDM) using a variety of syngeneic mouse tumors and compared immune responses in BCDM with those seen in wild type (WT) immunocompetent mice (ICM). A variety of murine tumors are rejected or inhibited in their growth in BCDM, compared with ICM, including the EL4 thymoma, and the MC38 colon carcinoma in C57BL/6 mice, as well as the EMT-6 breast carcinoma in BALB/c mice. In all three murine models, tumors show reduced growth in BCDM which is accompanied by increased T cell and NK cell infiltration, and a more vigorous Th1 cytokine response, and increased cytolytic T cell response in the absence of B cells. Reconstitution of the mice with B cells results in augmented tumor growth due to a diminished anti-tumor immune response and in reduction in CD8+ T cell and NK cell infiltration. Studies involving BCR transgenic mice indicated that B cells inhibit anti-tumor T cell responses through antigen non-specific mechanisms. More recent studies using the EMT-6 model demonstrated that both the number and function of Treg cells in ICM was increased relative to that seen in BCDM. Increased expansion of Treg cells was evident following EMT-6 implantation in ICM relative to that seen in non-tumor-bearing mice or BCDM the percentage and number of Tregs in spleen, tumor draining lymph nodes, and the tumor bed are increased in ICM compared with BCDM. Treg functional capacity as measured by suppression assays appears to be reduced in BCDM compared with ICM. In contrast to other described types of B regulatory activity, adoptive transfer of B cells can rescue tumor growth independently of the ability of B cells to secrete IL-10, and also independently of MHC-II expression. In experiments using the MC38 adenocarcinoma model, BCDM reconstituted with WT B cells support tumor growth while tumor growth continues to be inhibited in BCDM reconstituted with OX40L-/- B cells. This suggests that interaction between OX40 on T cells and OX40-ligand on B cells may be important in modulating anti-tumor immune response. Ongoing experiments in the laboratory indicate that B cells migrate to the site of tumor and acquire expression of immunosuppressive ligands and/or cytokines that contribute to the inhibition of anti-tumor immune response. Significant infiltration of human tumors by Treg cells as well as B cells suggests that observations made in murine systems may be applicable to human tumors as well.

Original languageEnglish
Pages (from-to)115-124
Number of pages10
JournalImmunologic Research
Volume57
Issue number1-3
DOIs
StatePublished - Dec 1 2013

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B-Lymphocytes
Neoplasms
T-Lymphocytes
Regulatory T-Lymphocytes
Growth
Natural Killer Cells
OX40 Ligand
Cytokines
Thymoma
Adoptive Transfer
Immunosuppressive Agents
Inbred C57BL Mouse
Interleukin-10
Transgenic Mice
Immunity
Colon
Adenocarcinoma
Spleen
Lymph Nodes
Breast Neoplasms

Keywords

  • Anti-tumor response
  • B cell suppression
  • B regulatory cell
  • T regulatory cell

ASJC Scopus subject areas

  • Immunology

Cite this

B cell regulation of anti-tumor immune response. / Zhang, Yu; Morgan, Richard; Podack, Eckhard R.; Rosenblatt, Joseph D.

In: Immunologic Research, Vol. 57, No. 1-3, 01.12.2013, p. 115-124.

Research output: Contribution to journalArticle

Zhang, Yu ; Morgan, Richard ; Podack, Eckhard R. ; Rosenblatt, Joseph D. / B cell regulation of anti-tumor immune response. In: Immunologic Research. 2013 ; Vol. 57, No. 1-3. pp. 115-124.
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