Tim4 enables large peritoneal macrophages to cross-present tumor antigens at early stages of tumorigenesis
Summary: Receptors controlling the cross-presentation of tumor antigens by macrophage subsets in cancer tissues are poorly explored. Here, we show that TIM4+ large peritoneal macrophages efficiently capture and cross-present tumor-associated antigens at early stages of peritoneal infiltration by ova...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724004248 |
| _version_ | 1797213408480722944 |
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| author | Sonal Joshi Lucía López Luciano Gastón Morosi Roberto Amadio Manendra Pachauri Marco Bestagno Ironya Paul Ogar Mauro Giacca Giulia Maria Piperno Daan Vorselen Federica Benvenuti |
| author_facet | Sonal Joshi Lucía López Luciano Gastón Morosi Roberto Amadio Manendra Pachauri Marco Bestagno Ironya Paul Ogar Mauro Giacca Giulia Maria Piperno Daan Vorselen Federica Benvenuti |
| author_sort | Sonal Joshi |
| collection | DOAJ |
| description | Summary: Receptors controlling the cross-presentation of tumor antigens by macrophage subsets in cancer tissues are poorly explored. Here, we show that TIM4+ large peritoneal macrophages efficiently capture and cross-present tumor-associated antigens at early stages of peritoneal infiltration by ovarian cancer cells. The phosphatidylserine (PS) receptor TIM4 promotes maximal uptake of dead cells or PS-coated artificial targets and triggers inflammatory and metabolic gene programs in combination with cytoskeletal remodeling and upregulation of transcriptional signatures related to antigen processing. At the cellular level, TIM4-mediated engulfment induces nucleation of F-actin around nascent phagosomes, delaying the recruitment of vacuolar ATPase, acidification, and cargo degradation. In vivo, TIM4 deletion blunts induction of early anti-tumoral effector CD8 T cells and accelerates the progression of ovarian tumors. We conclude that TIM4-mediated uptake drives the formation of specialized phagosomes that prolong the integrity of ingested antigens and facilitate cross-presentation, contributing to immune surveillance of the peritoneum. |
| first_indexed | 2024-04-24T10:57:48Z |
| format | Article |
| id | doaj.art-c2dde8a380ab4786a23705a24951b4bc |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-24T10:57:48Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-c2dde8a380ab4786a23705a24951b4bc2024-04-12T04:45:07ZengElsevierCell Reports2211-12472024-04-01434114096Tim4 enables large peritoneal macrophages to cross-present tumor antigens at early stages of tumorigenesisSonal Joshi0Lucía López1Luciano Gastón Morosi2Roberto Amadio3Manendra Pachauri4Marco Bestagno5Ironya Paul Ogar6Mauro Giacca7Giulia Maria Piperno8Daan Vorselen9Federica Benvenuti10Cellular Immunology, International Center for Genetic Engineering and Biotechnology (ICGEB), Trieste, ItalyCellular Immunology, International Center for Genetic Engineering and Biotechnology (ICGEB), Trieste, ItalyCellular Immunology, International Center for Genetic Engineering and Biotechnology (ICGEB), Trieste, ItalyCellular Immunology, International Center for Genetic Engineering and Biotechnology (ICGEB), Trieste, ItalyDepartment of Medical, Surgical, and Health Sciences, University of Trieste and International Center for Genetic Engineering and Biotechnology (ICGEB), Trieste, ItalyCellular Immunology, International Center for Genetic Engineering and Biotechnology (ICGEB), Trieste, ItalyCellular Immunology, International Center for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy; Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medical Sciences, University of Calabar, P.M.B. 1115 Calabar, Cross River State, NigeriaDepartment of Medical, Surgical, and Health Sciences, University of Trieste and International Center for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy; King’s College London, British Heart Foundation Center of Research Excellence, School of Cardiovascular Medicine & Sciences, London, UKCellular Immunology, International Center for Genetic Engineering and Biotechnology (ICGEB), Trieste, ItalyDepartment of Cell Biology & Immunology, Wageningen University & Research, 6708 PD Wageningen, the NetherlandsCellular Immunology, International Center for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy; Corresponding authorSummary: Receptors controlling the cross-presentation of tumor antigens by macrophage subsets in cancer tissues are poorly explored. Here, we show that TIM4+ large peritoneal macrophages efficiently capture and cross-present tumor-associated antigens at early stages of peritoneal infiltration by ovarian cancer cells. The phosphatidylserine (PS) receptor TIM4 promotes maximal uptake of dead cells or PS-coated artificial targets and triggers inflammatory and metabolic gene programs in combination with cytoskeletal remodeling and upregulation of transcriptional signatures related to antigen processing. At the cellular level, TIM4-mediated engulfment induces nucleation of F-actin around nascent phagosomes, delaying the recruitment of vacuolar ATPase, acidification, and cargo degradation. In vivo, TIM4 deletion blunts induction of early anti-tumoral effector CD8 T cells and accelerates the progression of ovarian tumors. We conclude that TIM4-mediated uptake drives the formation of specialized phagosomes that prolong the integrity of ingested antigens and facilitate cross-presentation, contributing to immune surveillance of the peritoneum.http://www.sciencedirect.com/science/article/pii/S2211124724004248CP: ImmunologyCP: Cancer |
| spellingShingle | Sonal Joshi Lucía López Luciano Gastón Morosi Roberto Amadio Manendra Pachauri Marco Bestagno Ironya Paul Ogar Mauro Giacca Giulia Maria Piperno Daan Vorselen Federica Benvenuti Tim4 enables large peritoneal macrophages to cross-present tumor antigens at early stages of tumorigenesis Cell Reports CP: Immunology CP: Cancer |
| title | Tim4 enables large peritoneal macrophages to cross-present tumor antigens at early stages of tumorigenesis |
| title_full | Tim4 enables large peritoneal macrophages to cross-present tumor antigens at early stages of tumorigenesis |
| title_fullStr | Tim4 enables large peritoneal macrophages to cross-present tumor antigens at early stages of tumorigenesis |
| title_full_unstemmed | Tim4 enables large peritoneal macrophages to cross-present tumor antigens at early stages of tumorigenesis |
| title_short | Tim4 enables large peritoneal macrophages to cross-present tumor antigens at early stages of tumorigenesis |
| title_sort | tim4 enables large peritoneal macrophages to cross present tumor antigens at early stages of tumorigenesis |
| topic | CP: Immunology CP: Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724004248 |
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