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PMID: 24909985 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

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

Cancer cell ·Vol. 25 ·No. 6 ·2014-06-16 ·Pages 809-821

Affara NI, Ruffell B, Medler TR, Gunderson AJ, Johansson M, Bornstein S, Bergsland E, Steinhoff M, Li Y, Gong Q, Ma Y, Wiesen JF, Wong MH, Kulesz-Martin M, Irving B, Coussens LM

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.

MeSH Terms
Animals Antineoplastic Combined Chemotherapy Protocols/therapeutic use B-Lymphocytes/drug effects,immunology,pathology CD8-Positive T-Lymphocytes/immunology,pathology CHO Cells Carcinoma, Squamous Cell/drug therapy,immunology,pathology Cricetulus Female Humans Lymphocytes, Tumor-Infiltrating/immunology,pathology Macrophages/drug effects,immunology,pathology Mice Mice, Transgenic Neoplasms/drug therapy,immunology,pathology Organoplatinum Compounds/administration & dosage Paclitaxel/administration & dosage Phenotype Tumor Microenvironment Xenograft Model Antitumor Assays
Chemicals
Organoplatinum Compounds Paclitaxel
Authors & Affiliations
16 authors, click to expand affiliations / ORCID
Affara Nesrine I
Department of Pathology, University of California, San Francisco, CA 94143, USA.
Ruffell Brian
Department of Pathology, University of California, San Francisco, CA 94143, USA. | Department of Cell and Developmental Biology, Oregon Health and Science University, Portland, OR 97239, USA. | Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA.
Medler Terry R
Department of Cell and Developmental Biology, Oregon Health and Science University, Portland, OR 97239, USA.
Gunderson Andrew J
Department of Cell and Developmental Biology, Oregon Health and Science University, Portland, OR 97239, USA.
Johansson Magnus
Department of Pathology, University of California, San Francisco, CA 94143, USA.
Bornstein Sophia
Department of Radiation Medicine, Oregon Health and Science University, Portland, OR 97239, USA.
Bergsland Emily
Department of Medicine, University of California, San Francisco, CA 94143, USA. | Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA.
Steinhoff Martin
Department of Dermatology, University of California, San Francisco, CA 94143, USA.
Li Yijin
Genentech, South San Francisco, CA 94080, USA.
Gong Qian
Genentech, South San Francisco, CA 94080, USA.
Ma Yan
Genentech, South San Francisco, CA 94080, USA.
Wiesen Jane F
Department of Pathology, University of California, San Francisco, CA 94143, USA. | Department of Cell and Developmental Biology, Oregon Health and Science University, Portland, OR 97239, USA.
Wong Melissa H
Department of Cell and Developmental Biology, Oregon Health and Science University, Portland, OR 97239, USA. | Department of Dermatology Oregon Health and Science University, Portland, OR 97239, USA. | Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA.
Kulesz-Martin Molly
Department of Cell and Developmental Biology, Oregon Health and Science University, Portland, OR 97239, USA. | Department of Dermatology Oregon Health and Science University, Portland, OR 97239, USA. | Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA.
Irving Bryan
Genentech, South San Francisco, CA 94080, USA.
Coussens Lisa M
Department of Pathology, University of California, San Francisco, CA 94143, USA. | Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA. | Department of Cell and Developmental Biology, Oregon Health and Science University, Portland, OR 97239, USA. | Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA.
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Article Info
Journal
Cancer cell
Abbr.
Cancer Cell
ISSN
1878-3686
DOI
10.1016/j.ccr.2014.04.026
Published
2014-06-16
Epub
2014-00-05
Pages
809-821
Language
English
Region
United States
NLM ID
101130617
PMCID
PMC4063283
Subset
IM
Grants
NCI NIH HHS · R01 CA155331 · United States
NCI NIH HHS · T32 CA106195 · United States
NCI NIH HHS · R01 CA140943 · United States
NIAID NIH HHS · T32AI078903-04 · United States
NCI NIH HHS · R01 CA130980 · United States
NCI NIH HHS · NCI P30CA069533 · United States
NIAID NIH HHS · T32 AI078903 · United States
NCI NIH HHS · T32CA106195 · United States
NCI NIH HHS · P30 CA069533 · United States
NCI NIH HHS · T32 CA108462 · United States
NCI NIH HHS · U54 CA163123 · United States
External Links
PubMed source DOI: 10.1016/j.ccr.2014.04.026 PMC Full Text View journal details
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