Cytotoxic NK Cells Impede Response to Checkpoint Immunotherapy in Melanoma with an Immune-Excluded Phenotype.
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| Format: | Artículo científico |
| Langue: | en |
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Cancer discovery
2025
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| _version_ | 1868266191318941696 |
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| author | Pozniak, Joanna Roda, Niccolò Landeloos, Ewout Antoranz, Asier Van Herck, Yannick De Visscher, Amber Demaerel, Philip Georg Vanwynsberghe, Lukas Declercq, Jeroen Gkemisis, Christos Bervoets, Greet Song, No-Joon Bassez, Ayse Browaeys, Robin Pollaris, Lotte Bosisio, Francesca M Boecxstaens, Veerle Saeys, Yvan Lambrechts, Diether Li, Zihai Matthys, Patrick Bechter, Oliver Marine, Jean-Christophe |
| author_facet | Pozniak, Joanna Roda, Niccolò Landeloos, Ewout Antoranz, Asier Van Herck, Yannick De Visscher, Amber Demaerel, Philip Georg Vanwynsberghe, Lukas Declercq, Jeroen Gkemisis, Christos Bervoets, Greet Song, No-Joon Bassez, Ayse Browaeys, Robin Pollaris, Lotte Bosisio, Francesca M Boecxstaens, Veerle Saeys, Yvan Lambrechts, Diether Li, Zihai Matthys, Patrick Bechter, Oliver Marine, Jean-Christophe Pozniak, Joanna Roda, Niccolò Landeloos, Ewout Antoranz, Asier Van Herck, Yannick De Visscher, Amber Demaerel, Philip Georg Vanwynsberghe, Lukas Declercq, Jeroen Gkemisis, Christos Bervoets, Greet Song, No-Joon Bassez, Ayse Browaeys, Robin Pollaris, Lotte Bosisio, Francesca M Boecxstaens, Veerle Saeys, Yvan Lambrechts, Diether Li, Zihai Matthys, Patrick Bechter, Oliver Marine, Jean-Christophe |
| collection | PubMed - marine biology |
| contents | Cytotoxic NK Cells Impede Response to Checkpoint Immunotherapy in Melanoma with an Immune-Excluded Phenotype. Pozniak, Joanna Roda, Niccolò Landeloos, Ewout Antoranz, Asier Van Herck, Yannick De Visscher, Amber Demaerel, Philip Georg Vanwynsberghe, Lukas Declercq, Jeroen Gkemisis, Christos Bervoets, Greet Song, No-Joon Bassez, Ayse Browaeys, Robin Pollaris, Lotte Bosisio, Francesca M Boecxstaens, Veerle Saeys, Yvan Lambrechts, Diether Li, Zihai Matthys, Patrick Bechter, Oliver Marine, Jean-Christophe Animals Killer Cells, Natural Melanoma Humans Mice Immune Checkpoint Inhibitors Phenotype Immunotherapy CD8-Positive T-Lymphocytes Female Immune checkpoint blockade (ICB) has revolutionized cancer treatment. Unfortunately, the inability of lymphocytes to infiltrate the tumor nest, a phenomenon known as immune exclusion, drastically limits ICB responsiveness. Analyzing the immune landscape of matched pre- and early on-treatment biopsies of patients with melanoma undergoing ICB therapy, we observed a significant increase in cytotoxic NK cells in early on-treatment biopsies from nonresponders. Spatial multiomic analyses revealed that, although NK cells colocalized with CD8+ T cells within the tumor bed in responding lesions, they were excluded from the tumor parenchyma in nonresponding lesions. Strikingly, pharmacologic depletion of NK cells in a unique melanoma mouse model exhibiting an immune-excluded phenotype unleashed immune infiltration of the tumor core and tumor clearance upon ICB exposure. Mechanistically, we show that NK cells are actively recruited to immune-excluded areas upon ICB exposure via the chemokine receptor CX3CR1 to suppress tumor infiltration and antitumor function of CD8+ T cells. Immune exclusion is responsible for intrinsic resistance to ICB in about half of nonresponder patients. Our unexpected observation that targeting NK cell biology unleashes the recruitment and antitumor activity of CD8+ T cells in tumors with an immune-excluded phenotype offers a potential therapeutic avenue for this large patient population. See related commentary by Galvez-Cancino et al., p. 1777 See related article by Song et al., p. 1835. |
| format | Artículo científico |
| id | pubmed_40530504 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | Cancer discovery |
| record_format | pubmed |
| spellingShingle | Cytotoxic NK Cells Impede Response to Checkpoint Immunotherapy in Melanoma with an Immune-Excluded Phenotype. Pozniak, Joanna Roda, Niccolò Landeloos, Ewout Antoranz, Asier Van Herck, Yannick De Visscher, Amber Demaerel, Philip Georg Vanwynsberghe, Lukas Declercq, Jeroen Gkemisis, Christos Bervoets, Greet Song, No-Joon Bassez, Ayse Browaeys, Robin Pollaris, Lotte Bosisio, Francesca M Boecxstaens, Veerle Saeys, Yvan Lambrechts, Diether Li, Zihai Matthys, Patrick Bechter, Oliver Marine, Jean-Christophe Animals Killer Cells, Natural Melanoma Humans Mice Immune Checkpoint Inhibitors Phenotype Immunotherapy CD8-Positive T-Lymphocytes Female Cytotoxic NK Cells Impede Response to Checkpoint Immunotherapy in Melanoma with an Immune-Excluded Phenotype. Pozniak, Joanna Roda, Niccolò Landeloos, Ewout Antoranz, Asier Van Herck, Yannick De Visscher, Amber Demaerel, Philip Georg Vanwynsberghe, Lukas Declercq, Jeroen Gkemisis, Christos Bervoets, Greet Song, No-Joon Bassez, Ayse Browaeys, Robin Pollaris, Lotte Bosisio, Francesca M Boecxstaens, Veerle Saeys, Yvan Lambrechts, Diether Li, Zihai Matthys, Patrick Bechter, Oliver Marine, Jean-Christophe Animals Killer Cells, Natural Melanoma Humans Mice Immune Checkpoint Inhibitors Phenotype Immunotherapy CD8-Positive T-Lymphocytes Female Immune checkpoint blockade (ICB) has revolutionized cancer treatment. Unfortunately, the inability of lymphocytes to infiltrate the tumor nest, a phenomenon known as immune exclusion, drastically limits ICB responsiveness. Analyzing the immune landscape of matched pre- and early on-treatment biopsies of patients with melanoma undergoing ICB therapy, we observed a significant increase in cytotoxic NK cells in early on-treatment biopsies from nonresponders. Spatial multiomic analyses revealed that, although NK cells colocalized with CD8+ T cells within the tumor bed in responding lesions, they were excluded from the tumor parenchyma in nonresponding lesions. Strikingly, pharmacologic depletion of NK cells in a unique melanoma mouse model exhibiting an immune-excluded phenotype unleashed immune infiltration of the tumor core and tumor clearance upon ICB exposure. Mechanistically, we show that NK cells are actively recruited to immune-excluded areas upon ICB exposure via the chemokine receptor CX3CR1 to suppress tumor infiltration and antitumor function of CD8+ T cells. Immune exclusion is responsible for intrinsic resistance to ICB in about half of nonresponder patients. Our unexpected observation that targeting NK cell biology unleashes the recruitment and antitumor activity of CD8+ T cells in tumors with an immune-excluded phenotype offers a potential therapeutic avenue for this large patient population. See related commentary by Galvez-Cancino et al., p. 1777 See related article by Song et al., p. 1835. |
| title | Cytotoxic NK Cells Impede Response to Checkpoint Immunotherapy in Melanoma with an Immune-Excluded Phenotype. |
| topic | Animals Killer Cells, Natural Melanoma Humans Mice Immune Checkpoint Inhibitors Phenotype Immunotherapy CD8-Positive T-Lymphocytes Female |
| url | https://pubmed.ncbi.nlm.nih.gov/40530504/ |