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.
Cancer Cell. 2014 Jun 16;25(6):809-821. doi: 10.1016/j.ccr.2014.04.026. Epub 2014 Jun 5.
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.
B 细胞通过在癌前组织中沉积含有免疫球蛋白的免疫复合物以及 Fcγ 受体依赖性激活髓样细胞来促进鳞状细胞癌 (SCC) 的发展。由于外阴和头颈部的人类 SCC 具有 B 细胞浸润的特征，我们检查了 B 细胞缺陷小鼠，发现对 SCC 生长的支持减少。虽然作为单一药物无效，但用 B 细胞耗竭 αCD20 单克隆抗体治疗患有预先存在 SCC 的小鼠可改善对铂类和紫杉醇为基础的化疗的反应。改善的化疗反应依赖于通过 CCR5 依赖性机制促进激活的 CD8(+)淋巴细胞浸润肿瘤的巨噬细胞改变趋化因子表达。这些数据表明 B 细胞及其下游调节的髓样细胞途径代表了在某些肿瘤中进行抗癌治疗的可行靶点。
