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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
Cancer cell
2026
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/41576931/ |
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| author | Karakousi, Triantafyllia Cristaldi, Vanessa Lopes de Oliveira, Maria Luiza Delclaux, Ines Besson, Naomi R Geraldo, Luiz Henrique González-Robles, Tania J McDonnough, Devyon R Martinez-Krams, Daniel da Silva, Gabrielle Breazeale, Alec P Encarnacion-Rosado, Joel Pozniak, Joanna Qiu, Shi Illa Bochaca, Irineu Kaiza, Medard E Kim, Hye Mi Bruno, Tullia C Reizis, Boris Moshiri, Ata S Kimmelman, Alec C Ruggles, Kelly V Osman, Iman Marine, Jean-Christophe Chandel, Navdeep S Lund, Amanda W |
| author_facet | Karakousi, Triantafyllia Cristaldi, Vanessa Lopes de Oliveira, Maria Luiza Delclaux, Ines Besson, Naomi R Geraldo, Luiz Henrique González-Robles, Tania J McDonnough, Devyon R Martinez-Krams, Daniel da Silva, Gabrielle Breazeale, Alec P Encarnacion-Rosado, Joel Pozniak, Joanna Qiu, Shi Illa Bochaca, Irineu Kaiza, Medard E Kim, Hye Mi Bruno, Tullia C Reizis, Boris Moshiri, Ata S Kimmelman, Alec C Ruggles, Kelly V Osman, Iman Marine, Jean-Christophe Chandel, Navdeep S Lund, Amanda W Karakousi, Triantafyllia Cristaldi, Vanessa Lopes de Oliveira, Maria Luiza Delclaux, Ines Besson, Naomi R Geraldo, Luiz Henrique González-Robles, Tania J McDonnough, Devyon R Martinez-Krams, Daniel da Silva, Gabrielle Breazeale, Alec P Encarnacion-Rosado, Joel Pozniak, Joanna Qiu, Shi Illa Bochaca, Irineu Kaiza, Medard E Kim, Hye Mi Bruno, Tullia C Reizis, Boris Moshiri, Ata S Kimmelman, Alec C Ruggles, Kelly V Osman, Iman Marine, Jean-Christophe Chandel, Navdeep S Lund, Amanda W |
| collection | PubMed - marine biology |
| contents | IFNγ-dependent metabolic reprogramming restrains an immature, pro-metastatic lymphatic state in melanoma. Karakousi, Triantafyllia Cristaldi, Vanessa Lopes de Oliveira, Maria Luiza Delclaux, Ines Besson, Naomi R Geraldo, Luiz Henrique González-Robles, Tania J McDonnough, Devyon R Martinez-Krams, Daniel da Silva, Gabrielle Breazeale, Alec P Encarnacion-Rosado, Joel Pozniak, Joanna Qiu, Shi Illa Bochaca, Irineu Kaiza, Medard E Kim, Hye Mi Bruno, Tullia C Reizis, Boris Moshiri, Ata S Kimmelman, Alec C Ruggles, Kelly V Osman, Iman Marine, Jean-Christophe Chandel, Navdeep S Lund, Amanda W Interferon-gamma Animals Metabolic Reprogramming Lymphatic Metastasis Melanoma Mice Lymphatic Vessels Humans Receptors, Interferon Interferon gamma Receptor Immunologic Surveillance Mitochondria Lymphangiogenesis Female Cell Line, Tumor Cell Proliferation Lymphatic vessels activate anti-tumor immune surveillance and support metastasis. Whether there are distinct lymphatic phenotypes that govern immunity and metastasis remains unclear. Here we reveal that cytotoxic immunity normalizes lymphatic function and uncouples immune and metastatic potential. We demonstrate that intratumoral lymphatic vessel density negatively correlates with cytotoxic immunity and that IFNγ reprograms the intratumoral lymphatic state. Lymphatic deletion of Ifngr1 expanded the intratumoral lymphatic network and drove the emergence of a tip-like state that promotes lymph node metastasis but not dendritic cell migration or response to immune checkpoint blockade (ICB). Mechanistically, IFNγ restrains proliferation and cell state programs through inhibition of mitochondrial respiration. Lymphatic-specific inhibition of mitochondrial complex III restrained the intratumoral tip-like state, blocked metastasis, and enhanced the response to ICB. Our data reveal that IFNγ induces a metabolic and phenotypic switch in tumor-associated lymphatic vessels that blocks regional metastasis and reinforces immune surveillance. |
| format | Artículo científico |
| id | pubmed_41576931 |
| institution | PubMed |
| language | en |
| publishDate | 2026 |
| publisher | Cancer cell |
| record_format | pubmed |
| spellingShingle | IFNγ-dependent metabolic reprogramming restrains an immature, pro-metastatic lymphatic state in melanoma. Karakousi, Triantafyllia Cristaldi, Vanessa Lopes de Oliveira, Maria Luiza Delclaux, Ines Besson, Naomi R Geraldo, Luiz Henrique González-Robles, Tania J McDonnough, Devyon R Martinez-Krams, Daniel da Silva, Gabrielle Breazeale, Alec P Encarnacion-Rosado, Joel Pozniak, Joanna Qiu, Shi Illa Bochaca, Irineu Kaiza, Medard E Kim, Hye Mi Bruno, Tullia C Reizis, Boris Moshiri, Ata S Kimmelman, Alec C Ruggles, Kelly V Osman, Iman Marine, Jean-Christophe Chandel, Navdeep S Lund, Amanda W Interferon-gamma Animals Metabolic Reprogramming Lymphatic Metastasis Melanoma Mice Lymphatic Vessels Humans Receptors, Interferon Interferon gamma Receptor Immunologic Surveillance Mitochondria Lymphangiogenesis Female Cell Line, Tumor Cell Proliferation IFNγ-dependent metabolic reprogramming restrains an immature, pro-metastatic lymphatic state in melanoma. Karakousi, Triantafyllia Cristaldi, Vanessa Lopes de Oliveira, Maria Luiza Delclaux, Ines Besson, Naomi R Geraldo, Luiz Henrique González-Robles, Tania J McDonnough, Devyon R Martinez-Krams, Daniel da Silva, Gabrielle Breazeale, Alec P Encarnacion-Rosado, Joel Pozniak, Joanna Qiu, Shi Illa Bochaca, Irineu Kaiza, Medard E Kim, Hye Mi Bruno, Tullia C Reizis, Boris Moshiri, Ata S Kimmelman, Alec C Ruggles, Kelly V Osman, Iman Marine, Jean-Christophe Chandel, Navdeep S Lund, Amanda W Interferon-gamma Animals Metabolic Reprogramming Lymphatic Metastasis Melanoma Mice Lymphatic Vessels Humans Receptors, Interferon Interferon gamma Receptor Immunologic Surveillance Mitochondria Lymphangiogenesis Female Cell Line, Tumor Cell Proliferation Lymphatic vessels activate anti-tumor immune surveillance and support metastasis. Whether there are distinct lymphatic phenotypes that govern immunity and metastasis remains unclear. Here we reveal that cytotoxic immunity normalizes lymphatic function and uncouples immune and metastatic potential. We demonstrate that intratumoral lymphatic vessel density negatively correlates with cytotoxic immunity and that IFNγ reprograms the intratumoral lymphatic state. Lymphatic deletion of Ifngr1 expanded the intratumoral lymphatic network and drove the emergence of a tip-like state that promotes lymph node metastasis but not dendritic cell migration or response to immune checkpoint blockade (ICB). Mechanistically, IFNγ restrains proliferation and cell state programs through inhibition of mitochondrial respiration. Lymphatic-specific inhibition of mitochondrial complex III restrained the intratumoral tip-like state, blocked metastasis, and enhanced the response to ICB. Our data reveal that IFNγ induces a metabolic and phenotypic switch in tumor-associated lymphatic vessels that blocks regional metastasis and reinforces immune surveillance. |
| title | IFNγ-dependent metabolic reprogramming restrains an immature, pro-metastatic lymphatic state in melanoma. |
| topic | Interferon-gamma Animals Metabolic Reprogramming Lymphatic Metastasis Melanoma Mice Lymphatic Vessels Humans Receptors, Interferon Interferon gamma Receptor Immunologic Surveillance Mitochondria Lymphangiogenesis Female Cell Line, Tumor Cell Proliferation |
| url | https://pubmed.ncbi.nlm.nih.gov/41576931/ |