Proinflammatory polarization strongly reduces human macrophage in vitro phagocytosis of tumor cells in response to CD47 blockade.
Cancer ⋅ Immunotherapy ⋅ Macrophages ⋅ Phagocytosis ⋅ Tumor immunology ⋅
Journal
European journal of immunology
ISSN: 1521-4141
Titre abrégé: Eur J Immunol
Pays: Germany
ID NLM: 1273201
Informations de publication
Date de publication:
09 Apr 2024
09 Apr 2024
Historique:
revised:
26
03
2024
received:
11
10
2023
accepted:
28
03
2024
medline:
9
4
2024
pubmed:
9
4
2024
entrez:
9
4
2024
Statut:
aheadofprint
Résumé
Antibody-based CD47 blockade aims to activate macrophage phagocytosis of tumor cells. However, macrophages possess a high degree of phenotype heterogeneity that likely influences phagocytic capacity. In murine models, proinflammatory (M1) activation increases macrophage phagocytosis of tumor cells, but in human models, results have been conflicting. Here, we investigated the effects of proinflammatory polarization on the phagocytic response of human monocyte-derived macrophages in an in vitro model. Using both flow cytometry-based and fluorescence live-cell imaging-based phagocytosis assays, we observed that mouse monoclonal anti-CD47 antibody (B6H12) induced monocyte-derived macrophage phagocytosis of cancer cells in vitro. Proinflammatory (M1) macrophage polarization with IFN-γ+LPS resulted in a severe reduction in phagocytic response to CD47 blockade. This reduction coincided with increased expression of the antiphagocytic membrane proteins LILRB1 and Siglec-10 but was not rescued by combination blockade of the corresponding ligands. However, matrix metalloproteinase inhibitors (TAPI-0 or GM6001) partly restored response to CD47 blockade in a dose-dependent manner. In summary, these data suggest that proinflammatory (M1) activation reduces phagocytic response to CD47 blockade in human monocyte-derived macrophages.
Identifiants
pubmed: 38593339
doi: 10.1002/eji.202350824
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2350824Subventions
Organisme : Danish Cancer Society with Holger J. Møller as the principal recipient
ID : R269-A15717
Informations de copyright
© 2024 The Authors. European Journal of Immunology published by Wiley‐VCH GmbH.
Références
Feng, M., Jiang, W., Kim, B. Y. S., Zhang, C. C., Fu, Y. X. and Weissman, I. L., Phagocytosis checkpoints as new targets for cancer immunotherapy. Nat. Rev. Cancer 2019.
Mantovani, A., Allavena, P., Marchesi, F. and Garlanda, C., Macrophages as tools and targets in cancer therapy. Nat. Rev. Drug Discovery 2022.
Cockram, T. O. J., Dundee, J. M., Popescu, A. S. and Brown, G. C., The phagocytic code regulating phagocytosis of mammalian cells. Front. Immunol. 2021. 12: 629979.
Advani, R., Flinn, I., Popplewell, L., Forero, A., Bartlett, N. L., Ghosh, N., Kline, J. et al., CD47 blockade by Hu5F9‐G4 and rituximab in non‐Hodgkin's lymphoma. N. Engl. J. Med. 2018. 379(18): 1711–1721.
Sallman, D. A., Al Malki, M. M., Asch, A. S., Wang, E. S., Jurcic, J. G., Bradley, T. J., Flinn, I. W. et al., Magrolimab in combination with azacitidine in patients with higher‐risk myelodysplastic syndromes: final results of a phase Ib study. J. Clin. Oncol. 2023. 41(15): 2815–2826.
Paul, B., Liedtke, M., Khouri, J., Rifkin, R., Gandhi, M. D., Kin, A., Levy, M. Y. et al., A phase II multi‐arm study of magrolimab combinations in patients with relapsed/refractory multiple myeloma. Future Oncol. 2023. 19(1): 7–17.
Mantovani, A., Sica, A., Sozzani, S., Allavena, P., Vecchi, A. and Locati, M., The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol 2004. 25(12): 677–686.
Demaria, O., Cornen, S., Daëron, M., Morel, Y., Medzhitov, R. and Vivier, E., Harnessing innate immunity in cancer therapy. Nature 2019. 574(7776): 45–56.
Feng, M., Chen, J. Y., Weissman‐Tsukamoto, R., Volkmer, J. P., Ho, P. Y., McKenna, K. M., Cheshier, S., et al., Macrophages eat cancer cells using their own calreticulin as a guide: roles of TLR and Btk. Proc. Nat. Acad. Sci. U.S.A. 2015. 112(7): 2145–2150.
Tang, Z., Davidson, D., Li, R., Zhong, M.‐C., Qian, J., Chen, J. and Veillette, A., Inflammatory macrophages exploit unconventional pro‐phagocytic integrins for phagocytosis and anti‐tumor immunity. Cell Rep. 2021. 37(11): 110111.
Kosaka, A., Ishibashi, K., Nagato, T., Kitamura, H., Fujiwara, Y., Yasuda, S., Nagata, M., et al., CD47 blockade enhances the efficacy of intratumoral STING‐targeting therapy by activating phagocytes. J. Exp. Med. 2021. 218(11).
Zhang, M., Hutter, G., Kahn, S. A., Azad, T. D., Gholamin, S., Xu, C. Y., Liu, J., et al., Anti‐CD47 treatment stimulates phagocytosis of glioblastoma by M1 and M2 polarized macrophages and promotes M1 polarized macrophages in vivo. PLoS One 2016. 11(4): e0153550.
Schulz, D., Severin, Y., Zanotelli, V. R. T. and Bodenmiller, B., In‐depth characterization of monocyte‐derived macrophages using a mass cytometry‐based phagocytosis assay. Sci. Rep. 2019. 9(1): 1925.
Leidi, M., Gotti, E., Bologna, L., Miranda, E., Rimoldi, M., Sica, A., Roncalli, M. et al., M2 macrophages phagocytose rituximab‐opsonized leukemic targets more efficiently than m1 cells in vitro. J. Immunol. 2009. 182(7): 4415–4422.
Backman, K. A. and Guyre, P. M., Gamma‐interferon inhibits Fc receptor II‐mediated phagocytosis of tumor cells by human macrophages. Cancer Res. 1994. 54(9): 2456–2461.
Wedekind, H., Walz, K., Buchbender, M., Rieckmann, T., Strasser, E., Grottker, F., Fietkau, R. et al., Head and neck tumor cells treated with hypofractionated irradiation die via apoptosis and are better taken up by M1‐like macrophages. Strahlenther. Onkol. 2022. 198(2): 171–182.
Barkal, A. A., Weiskopf, K., Kao, K. S., Gordon, S. R., Rosental, B., Yiu, Y. Y., George, B. M., et al., Engagement of MHC class I by the inhibitory receptor LILRB1 suppresses macrophages and is a target of cancer immunotherapy. Nat. Immunol. 2018. 19(1): 76–84.
Barkal, A. A., Brewer, R. E., Markovic, M., Kowarsky, M., Barkal, S. A., Zaro, B. W., Krishnan, V. et al., CD24 signalling through macrophage Siglec‐10 is a target for cancer immunotherapy. Nature 2019. 572(7769): 392–396.
Park, M., Raftery, M. J., Thomas, P. S., Geczy, C. L., Bryant, K. and Tedla, N., Leukocyte immunoglobulin‐like receptor B4 regulates key signalling molecules involved in FcγRI‐mediated clathrin‐dependent endocytosis and phagocytosis. Sci. Rep. 2016. 6(1): 35085.
Sharma, N., Atolagbe, O. T., Ge, Z. and Allison, J. P., LILRB4 suppresses immunity in solid tumors and is a potential target for immunotherapy. J. Exp. Med. 2021. 218(7).
Barrett, T., Wilhite, S. E., Ledoux, P., Evangelista, C., Kim, I. F., Tomashevsky, M., Marshall, K. A. et al., NCBI GEO: archive for functional genomics data sets—update. Nucleic Acids Res. 2012. 41(D1): D991–D995.
Londino, J. D., Gulick, D., Isenberg, J. S. and Mallampalli, R. K., Cleavage of signal regulatory protein α (SIRPα) enhances inflammatory signaling. J. Biol. Chem. 2015. 290(52): 31113–31125.
Vladimirova, Y. V., Mølmer, M. K., Antonsen, K. W., Møller, N., Rittig, N., Nielsen, M. C. and Møller, H. J., A new serum macrophage checkpoint biomarker for innate immunotherapy: soluble signal‐regulatory protein alpha (sSIRPα). Biomolecules 2022. 12(7): 937.
Etzerodt, A., Maniecki, M. B., Møller, K., Møller, H. J. and Moestrup, S. K., Tumor necrosis factor α‐converting enzyme (TACE/ADAM17) mediates ectodomain shedding of the scavenger receptor CD163. J. Leukoc. Biol. 2010. 88(6): 1201–1205.
Ma, J., Kummarapurugu, A. B., Hawkridge, A., Ghosh, S., Zheng, S. and Voynow, J. A., Neutrophil elastase‐regulated macrophage sheddome/secretome and phagocytic failure. Am. J. Physiol. Lung Cell. Mol. Physiol. 2021. 321(3): L555–L565.
Spiller, K. L., Wrona, E. A., Romero‐Torres, S., Pallotta, I., Graney, P. L., Witherel, C. E., Panicker, L. M. et al., Differential gene expression in human, murine, and cell line‐derived macrophages upon polarization. Exp. Cell. Res. 2016. 347(1): 1–13.
Tarique, A. A., Logan, J., Thomas, E., Holt, P. G., Sly, P. D. and Fantino, E., Phenotypic, functional, and plasticity features of classical and alternatively activated human macrophages. Am. J. Respir. Cell Mol. Biol. 2015. 53(5): 676–688.
Frausto‐Del‐Río, D., Soto‐Cruz, I., Garay‐Canales, C., Ambriz, X., Soldevila, G., Carretero‐Ortega, J., Vázquez‐Prado, J. and Ortega, E., Interferon gamma induces actin polymerization, Rac1 activation and down regulates phagocytosis in human monocytic cells. Cytokine 2012. 57(1): 158–168.
Speert, D. P. and Thorson, L., Suppression by human recombinant gamma interferon of in vitro macrophage nonopsonic and opsonic phagocytosis and killing. Infect. Immun. 1991. 59(6): 1893–1898.
Schlesinger, L. S. and Horwitz, M. A., Phagocytosis of Mycobacterium leprae by human monocyte‐derived macrophages is mediated by complement receptors CR1 (CD35), CR3 (CD11b/CD18), and CR4 (CD11c/CD18) and IFN‐gamma activation inhibits complement receptor function and phagocytosis of this bacterium. J. Immunol. 1991. 147(6): 1983–1994.
Capsoni, F., Minonzio, F., Ongari, A. M., Bonara, P., Pinto, G., Carbonelli, V., Lazzarin, A. and Zanussi, C., Fc receptors expression and function in mononuclear phagocytes from AIDS patients: modulation by IFN‐gamma. Scand. J. Immunol. 1994. 39(1): 45–50.
Costales, P., Castellano, J., Revuelta‐López, E., Cal, R., Aledo, R., Llampayas, O., Nasarre, L. et al., Lipopolysaccharide downregulates CD91/low‐density lipoprotein receptor‐related protein 1 expression through SREBP‐1 overexpression in human macrophages. Atherosclerosis 2013. 227(1): 79–88.
Nagelkerke, S. Q., Dekkers, G., Kustiawan, I., Van De Bovenkamp, F. S., Geissler, J., Plomp, R., Wuhrer, M. et al., Inhibition of FcγR‐mediated phagocytosis by IVIg is independent of IgG‐Fc sialylation and FcγRIIb in human macrophages. Blood 2014. 124(25): 3709–3718.
Sauter, A., Yi, D. H., Li, Y., Roersma, S. and Appel, S., The culture dish surface influences the phenotype and cytokine production of human monocyte‐derived dendritic cells. Front. Immunol. 2019. 10: 2352.
Nielsen, M. C., Andersen, M. N. and Moller, H. J., Monocyte isolation techniques significantly impact the phenotype of both isolated monocytes and derived macrophages in vitro. Immunology 2019.
Chen, S., So, E. C., Strome, S. E. and Zhang, X., Impact of detachment methods on M2 macrophage phenotype and function. J. Immunol. Methods 2015. 426: 56–61.
Rey‐Giraud, F., Hafner, M. and Ries, C. H., In vitro generation of monocyte‐derived macrophages under serum‐free conditions improves their tumor promoting functions. PLoS One 2012. 7(8): e42656.
Antonsen, K. W., Friis, H. N., Sorensen, B. S., Etzerodt, A., Moestrup, S. K. and Møller, H. J., Comparison of culture media reveals that non‐essential amino acids strongly affect the phenotype of human monocyte‐derived macrophages. Immunology 2023.
Lacey, D. C., Achuthan, A., Fleetwood, A. J., Dinh, H., Roiniotis, J., Scholz, G. M., Chang, M. W. et al., Defining GM‐CSF‐ and macrophage‐CSF‐dependent macrophage responses by in vitro models. J. Immunol. 2012. 188(11): 5752–5765.
Andersen, C. L., Jensen, J. L. and Ørntoft, T. F., Normalization of real‐time quantitative reverse transcription‐PCR data: a model‐based variance estimation approach to identify genes suited for normalization, applied to bladder and colon cancer data sets. Cancer Res. 2004. 64(15): 5245–5250.
Møller, H. J., Hald, K. and Moestrup, S. K., Characterization of an enzyme‐linked immunosorbent assay for soluble CD163. Scand. J. Clin. Lab. Invest. 2002. 62(4): 293–299.
Andersen, M. N., Al‐Karradi, S. N., Kragstrup, T. W. and Hokland, M., Elimination of erroneous results in flow cytometry caused by antibody binding to Fc receptors on human monocytes and macrophages. Cytometry A 2016. 89(11): 1001–1009.
Cossarizza, A., Chang, H. D., Radbruch, A., Acs, A., Adam, D., Adam‐Klages, S., Agace, W. W. et al., Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition). Eur. J. Immunol. 2019. 49(10): 1457–1973.
Schindelin, J., Arganda‐Carreras, I., Frise, E., Kaynig, V., Longair, M., Pietzsch, T., Preibisch, S. et al., Fiji: an open‐source platform for biological‐image analysis. Nat. Methods 2012. 9(7): 676–682.