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.
Copyright © 2014 Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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B-Lymphocytes / drug effects
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B-Lymphocytes / immunology*
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B-Lymphocytes / pathology
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / pathology
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CHO Cells
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Carcinoma, Squamous Cell / drug therapy*
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Carcinoma, Squamous Cell / immunology*
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Carcinoma, Squamous Cell / pathology
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Cricetulus
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Female
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Humans
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Lymphocytes, Tumor-Infiltrating / immunology
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Lymphocytes, Tumor-Infiltrating / pathology
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Macrophages / drug effects
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Macrophages / immunology*
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Macrophages / pathology
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Mice
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Mice, Transgenic
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Neoplasms / drug therapy*
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Neoplasms / immunology*
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Neoplasms / pathology
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Organoplatinum Compounds / administration & dosage
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Paclitaxel / administration & dosage
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Phenotype
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Tumor Microenvironment
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Xenograft Model Antitumor Assays
Substances
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Organoplatinum Compounds
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Paclitaxel