Tumor location determines tissue-specific recruitment of tumor-associated macrophages and antibody-dependent immunotherapy response

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Science Immunology  06 Jan 2017:
Vol. 2, Issue 7, eaah6413
DOI: 10.1126/sciimmunol.aah6413

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TAMpering with tumors

Immunotherapeutic antibodies are a promising cancer therapy, but little is known about the nontargeted effects of these antibodies on immune cells through Fc receptor binding. Tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs), which have been implicated in both promoting and inhibiting tumor growth, express abundant Fcγ receptors. Lehmann et al. examined these cells in tumors growing in different sites—skin and lung. They found that the organ environment in which a tumor grows determined which TAM and TAN subpopulations contributed to antibody-dependent tumor immunotherapy. Different cellular pathways underlay the antibody response in different tissues. These data may help fine-tune therapeutic strategies to target cells that promote tumors and not those that fight them.


Despite recent advances in activating immune cells to target tumors, the presence of some immune cells, such as tumor-associated macrophages (TAMs) or tumor-associated neutrophils (TANs), may promote rather than inhibit tumor growth. However, it remains unclear how antibody-dependent tumor immunotherapies, such as cytotoxic or checkpoint control antibodies, affect different TAM or TAN populations, which abundantly express activating Fcγ receptors. In this study, we show that the tissue environment determines which cellular effector pathways are responsible for antibody-dependent tumor immunotherapy. Although TAMs derived from Ly6Chigh monocytes recruited by the CCL2-CCR2 axis were critical for tumor immunotherapy of skin tumors, the destruction of lung tumors was CCL2-independent and required the presence of colony-stimulating factor 2–dependent tissue-resident macrophages. Our findings suggest that TAMs may have a dual role not only in promoting tumor growth in certain tissue environments on the one hand but also in contributing to tumor cell destruction during antibody-mediated immunotherapy on the other hand.

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