[PDF][PDF] B cells regulate macrophage phenotype and response to chemotherapy in squamous carcinomas

NI Affara, B Ruffell, TR Medler, AJ Gunderson… - Cancer cell, 2014 - cell.com
NI Affara, B Ruffell, TR Medler, AJ Gunderson, M Johansson, S Bornstein, E Bergsland…
Cancer cell, 2014cell.com
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 …
Summary
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.
cell.com