Using the same melanoma cell line orthotopically implanted in different tissues, Lehmann et al. found that antibody-dependent control of melanoma in the skin required TAMs derived from Ly6Chigh monocytes recruited from blood via the CCL2-CCR2 axis, while control in the lung required CSF-2-dependent, tissue-resident alveolar macrophages.
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 Fcgamma 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.
Author Info: (1) Chair of Genetics, Department of Biology, University of Erlangen-Nuremberg, Erwin-Rommel-Str. 3, 91058 Erlangen, Germany. (2) Chair of Genetics, Department of Biology, Universi
Author Info: (1) Chair of Genetics, Department of Biology, University of Erlangen-Nuremberg, Erwin-Rommel-Str. 3, 91058 Erlangen, Germany. (2) Chair of Genetics, Department of Biology, University of Erlangen-Nuremberg, Erwin-Rommel-Str. 3, 91058 Erlangen, Germany. (3) Chair of Genetics, Department of Biology, University of Erlangen-Nuremberg, Erwin-Rommel-Str. 3, 91058 Erlangen, Germany. (4) Chair of Genetics, Department of Biology, University of Erlangen-Nuremberg, Erwin-Rommel-Str. 3, 91058 Erlangen, Germany. (5) Chair of Genetics, Department of Biology, University of Erlangen-Nuremberg, Erwin-Rommel-Str. 3, 91058 Erlangen, Germany. (6) Department of Dermatology, University Hospital Erlangen, 91054 Erlangen, Germany. (7) Department of Infection Biology, University Hospital Erlangen, Wasserturmstr. 3/5, 91054 Erlangen, Germany. (8) Chair of Genetics, Department of Biology, University of Erlangen-Nuremberg, Erwin-Rommel-Str. 3, 91058 Erlangen, Germany. (9) Department of Dermatology, University Hospital Erlangen, 91054 Erlangen, Germany. (10) Department of Dermatology, University Hospital Erlangen, 91054 Erlangen, Germany. (11) Department of Surgery, University Hospital Erlangen, Krankenhausstr. 12, 91054 Erlangen, Germany. (12) Department of Surgery, University Hospital Erlangen, Krankenhausstr. 12, 91054 Erlangen, Germany. (13) Chair of Genetics, Department of Biology, University of Erlangen-Nuremberg, Erwin-Rommel-Str. 3, 91058 Erlangen, Germany. falk.nimmerjahn@fau.de.
