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Cancer Cell. 2014 Jun 16;25(6):809-821. doi: 10.1016/j.ccr.2014.04.026. Epub 2014 Jun 5.

B cells regulate macrophage phenotype and response to chemotherapy in squamous carcinomas.

Author information

1
Department of Pathology, University of California, San Francisco, CA 94143, USA.
2
Department of Cell and Developmental Biology, Oregon Health and Science University, Portland, OR 97239, USA.
3
Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA.
4
Department of Radiation Medicine, Oregon Health and Science University, Portland, OR 97239, USA.
5
Department of Medicine, University of California, San Francisco, CA 94143, USA.
6
Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA.
7
Department of Dermatology, University of California, San Francisco, CA 94143, USA.
8
Genentech, South San Francisco, CA 94080, USA.
9
Department of Dermatology Oregon Health and Science University, Portland, OR 97239, USA.
#
Contributed equally

Abstract

B cells foster squamous cell carcinoma (SCC) development through deposition of immunoglobulin-containing immune complexes in premalignant tissue and Fcγ receptor-dependent activation of myeloid cells. Because human SCCs of the vulva and head and neck exhibited hallmarks of B cell infiltration, we examined B cell-deficient mice and found reduced support for SCC growth. Although ineffective as a single agent, treatment of mice bearing preexisting SCCs with B cell-depleting αCD20 monoclonal antibodies improved response to platinum- and Taxol-based chemotherapy. Improved chemoresponsiveness was dependent on altered chemokine expression by macrophages that promoted tumor infiltration of activated CD8(+) lymphocytes via CCR5-dependent mechanisms. These data reveal that B cells, and the downstream myeloid-based pathways they regulate, represent tractable targets for anticancer therapy in select tumors.

PMID:
24909985
PMCID:
PMC4063283
DOI:
10.1016/j.ccr.2014.04.026
[Indexed for MEDLINE]
Free PMC Article

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