Specific targeting of CD163+ TAMs mobilizes inflammatory monocytes and promotes T cell-mediated tumor regression

Anders Etzerodt, Kyriaki Tsalkitzi, Maciej Maniecki, William Damsky, Marcello Delfini, Elodie Baudoin, Morgane Moulin, Marcus Bosenberg, Jonas Heilskov Graversen, Nathalie Auphan-Anezin, Søren Kragh Moestrup, Toby Lawrence*

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Abstrakt

Tumor-associated macrophages (TAMs) play critical roles in tumor progression but are also capable of contributing to antitumor immunity. Recent studies have revealed an unprecedented heterogeneity among TAMs in both human cancer and experimental models. Nevertheless, we still understand little about the contribution of different TAM subsets to tumor progression. Here, we demonstrate that CD163-expressing TAMs specifically maintain immune suppression in an experimental model of melanoma that is resistant to anti-PD-1 checkpoint therapy. Specific depletion of the CD163+ macrophages results in a massive infiltration of activated T cells and tumor regression. Importantly, the infiltration of cytotoxic T cells was accompanied by the mobilization of inflammatory monocytes that significantly contributed to tumor regression. Thus, the specific targeting of CD163+ TAMs reeducates the tumor immune microenvironment and promotes both myeloid and T cell-mediated antitumor immunity, illustrating the importance of selective targeting of tumor-associated myeloid cells in a therapeutic context.

OriginalsprogEngelsk
TidsskriftThe Journal of Experimental Medicine
Vol/bind216
Udgave nummer10
Sider (fra-til)2394-2411
ISSN0022-1007
DOI
StatusUdgivet - 7. okt. 2019

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    Etzerodt, A., Tsalkitzi, K., Maniecki, M., Damsky, W., Delfini, M., Baudoin, E., Moulin, M., Bosenberg, M., Graversen, J. H., Auphan-Anezin, N., Moestrup, S. K., & Lawrence, T. (2019). Specific targeting of CD163+ TAMs mobilizes inflammatory monocytes and promotes T cell-mediated tumor regression. The Journal of Experimental Medicine, 216(10), 2394-2411. https://doi.org/10.1084/jem.20182124