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Cancer cell plasticity defines response to immunotherapy in cutaneous squamous cell carcinoma

Authors :
Laura Lorenzo-Sanz
Marta Lopez-Cerda
Victoria da Silva-Diz
Marta H. Artés
Sandra Llop
Rosa M. Penin
Josep Oriol Bermejo
Eva Gonzalez-Suarez
Manel Esteller
Francesc Viñals
Enrique Espinosa
Marc Oliva
Josep M. Piulats
Juan Martin-Liberal
Purificación Muñoz
Source :
Nature Communications, Vol 15, Iss 1, Pp 1-18 (2024)
Publication Year :
2024
Publisher :
Nature Portfolio, 2024.

Abstract

Abstract 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.

Subjects

Subjects :
Science

Details

Language :
English
ISSN :
20411723
Volume :
15
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Nature Communications
Publication Type :
Academic Journal
Accession number :
edsdoj.6c15c4009def405287d24b7b6ae51b70
Document Type :
article
Full Text :
https://doi.org/10.1038/s41467-024-49718-8