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| Pàgina inicial > Articles > Articles publicats > Cancer cell plasticity defines response to immunotherapy in cutaneous squamous cell carcinoma |
(Institut d'Investigació Biomèdica de Bellvitge) (Institut d'Investigació Biomèdica de Bellvitge) (Hospital Universitari de Bellvitge) (Centro Nacional de Investigaciones Oncológicas) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Institut Català d'Oncologia) (Hospital Universitario La Paz (Madrid)) (Institut Català d'Oncologia) (Medical Oncology Department. Catalan Institute of Oncology (ICO)) (Institut d'Investigació Biomèdica de Bellvitge)
| Data: | 2024 |
| Resum: | Immune checkpoint blockade (ICB) approaches have changed the therapeutic landscape for many tumor types. However, half of cutaneous squamous cell carcinoma (cSCC) patients remain unresponsive or develop resistance. Here, we show that, during cSCC progression in male mice, cancer cells acquire epithelial/mesenchymal plasticity and change their immune checkpoint (IC) ligand profile according to their features, dictating the IC pathways involved in immune evasion. Epithelial cancer cells, through the PD-1/PD-L1 pathway, and mesenchymal cancer cells, through the CTLA-4/CD80 and TIGIT/CD155 pathways, differentially block antitumor immune responses and determine the response to ICB therapies. Accordingly, the anti-PD-L1/TIGIT combination is the most effective strategy for blocking the growth of cSCCs that contain both epithelial and mesenchymal cancer cells. The expression of E-cadherin/Vimentin/CD80/CD155 proteins in cSCC, HNSCC and melanoma patient samples predicts response to anti-PD-1/PD-L1 therapy. Collectively, our findings indicate that the selection of ICB therapies should take into account the epithelial/mesenchymal features of cancer cells. |
| Ajuts: | Agencia Estatal de Investigación SAF2017-84976R Agencia Estatal de Investigación PID2020-113495RB-I00 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-595 Agència de Gestió d'Ajuts Universitaris i de Recerca 2021/SGR-00769 |
| Nota: | L.L.-S. received an IDIBELL Fellowship and an EMBO Short-Term Fellowship (number 7192); M.L.-C. was supported by the FI program (2019FI_B_00265) of the Secretariat for Universities and Research of the Department of Business and Knowledge of the Government of Catalonia, with the support of the European Social Fund (ESF) \u201CESF, Investing in your future\u201D; V.d.S.-D. was funded by a Spanish Ministry of Science and Innovation Fellowship. The research of P.M.\u2019s group is supported by the Spanish Ministry of Economy and Competitiveness MINECO (SAF2017-84976R and PID2020-113495RB-I00; co-funded by the FEDER funds/European Regional Development Fund (ERDF) - A way to build Europe), Fundaci\u00F3 Vallformosa and GESCO Family, and by the Catalan Department of Health (CERCA, Generalitat de Catalunya, 2017SGR595, 2021 SGR00769). J.M.-L. and P.M. acknowledge funding from Beca GEM (Grupo Espa\u00F1ol Multidisciplinar de Melanoma). We also thank the patients who enrolled in this study for their participation; the Tumor Biobank of the Bellvitge University Hospital and the IdiPAZ Biobank for their help collecting patients\u2019 tumor specimens; and the staff at the IDIBELL biostatistics, optical microscopy, and animal facilities, and at the UB/PCB flow cytometry facility for assistance. Figures\u00A01 c, 3 a and 4a were created with BioRender.com, released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license. |
| Nota: | L.L.-S. received an IDIBELL Fellowship and an EMBO Short-Term Fellowship (number 7192); M.L.-C. was supported by the FI program (2019FI_B_00265) of the Secretariat for Universities and Research of the Department of Business and Knowledge of the Government of Catalonia, with the support of the European Social Fund (ESF) \u201CESF, Investing in your future\u201D; V.d.S.-D. was funded by a Spanish Ministry of Science and Innovation Fellowship. The research of P.M.\u2019s group is supported by the Spanish Ministry of Economy and Competitiveness MINECO (SAF2017-84976R and PID2020-113495RB-I00; co-funded by the FEDER funds/European Regional Development Fund (ERDF) - A way to build Europe), Fundaci\u00F3 Vallformosa and GESCO Family, and by the Catalan Department of Health (CERCA, Generalitat de Catalunya, 2017SGR595, 2021 SGR00769). J.M.-L. and P.M. acknowledge funding from Beca GEM (Grupo Espa\u00F1ol Multidisciplinar de Melanoma). We also thank the patients who enrolled in this study for their participation; the Tumor Biobank of the Bellvitge University Hospital and the IdiPAZ Biobank for their help collecting patients\u2019 tumor specimens; and the staff at the IDIBELL biostatistics, optical microscopy, and animal facilities, and at the UB/PCB flow cytometry facility for assistance. Figures c, a and were created with BioRender.com, released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license. |
| Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Llengua: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Matèria: | Animals ; B7-1 Antigen ; B7-H1 Antigen ; Carcinoma, Squamous Cell ; Cell Line, Tumor ; Cell Plasticity ; CTLA-4 Antigen ; Epithelial-Mesenchymal Transition ; Humans ; Immune Checkpoint Inhibitors ; Immunotherapy ; Male ; Mice ; Programmed Cell Death 1 Receptor ; Receptors, Immunologic ; Receptors, Virus ; Skin Neoplasms |
| Publicat a: | Nature communications, Vol. 15 Núm. 1 (december 2024) , p. 5352, ISSN 2041-1723 |
