title: B cells regulate macrophage phenotype and response to chemotherapy in squamous carcinomas.
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.
authors.affiliation: Department of Pathology, University of California, San Francisco, CA 94143, USA.
authors.forename: Nesrine I
authors.initials: NI
authors.lastname: Affara
authors.affiliation: 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.
authors.forename: Brian
authors.initials: B
authors.lastname: Ruffell
authors.affiliation: Department of Cell and Developmental Biology, Oregon Health and Science University, Portland, OR 97239, USA.
authors.forename: Terry R
authors.initials: TR
authors.lastname: Medler
authors.affiliation: Department of Cell and Developmental Biology, Oregon Health and Science University, Portland, OR 97239, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Gunderson
authors.affiliation: Department of Pathology, University of California, San Francisco, CA 94143, USA.
authors.forename: Magnus
authors.initials: M
authors.lastname: Johansson
authors.affiliation: Department of Radiation Medicine, Oregon Health and Science University, Portland, OR 97239, USA.
authors.forename: Sophia
authors.initials: S
authors.lastname: Bornstein
authors.affiliation: 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.
authors.forename: Emily
authors.initials: E
authors.lastname: Bergsland
authors.affiliation: Department of Dermatology, University of California, San Francisco, CA 94143, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Steinhoff
authors.affiliation: Genentech, South San Francisco, CA 94080, USA.
authors.forename: Yijin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Genentech, South San Francisco, CA 94080, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Gong
authors.affiliation: Genentech, South San Francisco, CA 94080, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: 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.
authors.forename: Jane F
authors.initials: JF
authors.lastname: Wiesen
authors.affiliation: 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.
authors.forename: Melissa H
authors.initials: MH
authors.lastname: Wong
authors.affiliation: 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.
authors.forename: Molly
authors.initials: M
authors.lastname: Kulesz-Martin
authors.affiliation: Genentech, South San Francisco, CA 94080, USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Irving
authors.affiliation: 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.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Coussens
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D016466:CHO Cells; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D003412:Cricetulus; D005260:Female; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D017239:Paclitaxel / Q000008:administration & dosage; D010641:Phenotype; D059016:Tumor Microenvironment; D023041:Xenograft Model Antitumor Assays
chemical_list: D009944:Organoplatinum Compounds; D017239:Paclitaxel