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

doi:10.1084/jem.20182124

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

Inflammation Biology

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Abstract

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.

Original language	English
Pages (from-to)	2394-2411
Number of pages	18
Journal	The Journal of experimental medicine
Volume	216
Issue number	10
Early online date	2 Aug 2019
DOIs	https://doi.org/10.1084/jem.20182124
Publication status	Published - 7 Oct 2019

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10.1084/jem.20182124Licence: CC BY-NC-SA

Specific targeting of CD163+_ETZERODT_Accepted15July2019Publishedonline2August2019_GOLD VoRFinal published version, 4.82 MBLicence: CC BY-NC-SA

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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

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

abstract = "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.",

author = "Anders Etzerodt and Kyriaki Tsalkitzi and Maciej Maniecki and William Damsky and Marcello Delfini and Elodie Baudoin and Morgane Moulin and Marcus Bosenberg and Graversen, {Jonas Heilskov} and Nathalie Auphan-Anezin and Moestrup, {S{\o}ren Kragh} and Toby Lawrence",

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Etzerodt, A, Tsalkitzi, K, Maniecki, M, Damsky, W, Delfini, M, Baudoin, E, Moulin, M, Bosenberg, M, Graversen, JH, Auphan-Anezin, N, Moestrup, SK & Lawrence, T 2019, 'Specific targeting of CD163⁺ TAMs mobilizes inflammatory monocytes and promotes T cell-mediated tumor regression', The Journal of experimental medicine, vol. 216, no. 10, pp. 2394-2411. https://doi.org/10.1084/jem.20182124

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T1 - Specific targeting of CD163+ TAMs mobilizes inflammatory monocytes and promotes T cell-mediated tumor regression

AU - Etzerodt, Anders

AU - Tsalkitzi, Kyriaki

AU - Maniecki, Maciej

AU - Damsky, William

AU - Delfini, Marcello

AU - Baudoin, Elodie

AU - Moulin, Morgane

AU - Bosenberg, Marcus

AU - Graversen, Jonas Heilskov

AU - Auphan-Anezin, Nathalie

AU - Moestrup, Søren Kragh

AU - Lawrence, Toby

PY - 2019/10/7

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N2 - 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.

AB - 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.

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

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