B cell regulation of antitumor response

Ahmed Al Bayati, Yu Zhang, Joseph D. Rosenblatt

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

While the role of CD4+ T cells, cytolytic T cells, natural killer cells, and Th1 response in antitumor immunity has been appreciated for decades, a variety of human and murine tumors are heavily infiltrated with cells of B cell lineage. In contrast to the well-characterized role of T cells and adaptive immunity and of NK cells and the innate response in tumor rejection, as well as the suppressive role played by T-regulatory cells (Tregs), the role of B cells in the regulation of antitumor immunity is poorly understood. Increasing evidence points to a potential role of B cells in the suppression of immune responses in the context of malignancy. This includes a variety of murine models in which B cell infiltration has been associated with increased tumor growth, and even carcinogenesis, and the identification of subsets of B cells with unique regulatory properties. Several mechanisms have been implicated in B cell-mediated regulation of immune response. This includes preferential polarization of B cells along Th1 or Th2 pathways, the elaboration of immunosuppressive cytokines such as TGF-β and interleukin-10, B cell display of immunosuppressive co-stimulatory ligands such as CD86 and PD-L1, and/or B cell support for the development of Tregs within the tumor microenvironment. Evidence is also accumulating that malignant lymphoma and leukemia B cells may distort the balance between Tregs and so-called Th17 cells leading to a tumor microenvironment that is more conducive to lymphoma growth. The ability to target and even eradicate both normal and malignant B cells using monoclonal antibodies to CD19 and CD20 and using other means in the clinic suggest that B cell depletion may facilitate an antitumor immune response. Understanding mechanisms underlying B cell regulation of antitumor responses is therefore of paramount importance in developing new strategies for exploitation of antitumor immunity, and B cell-directed strategies may be applicable to both solid and lymphoid tumors.

Original languageEnglish (US)
Title of host publicationCancer Immunology
Subtitle of host publicationBench to Bedside Immunotherapy of Cancers
PublisherSpringer Berlin Heidelberg
Pages283-292
Number of pages10
ISBN (Electronic)9783662449462
ISBN (Print)9783662449455
DOIs
StatePublished - Jan 1 2015

ASJC Scopus subject areas

  • Medicine(all)
  • Immunology and Microbiology(all)

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