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

被引:2
作者
Lorenzo-Sanz, Laura [1 ]
Lopez-Cerda, Marta [1 ]
da Silva-Diz, Victoria [1 ,12 ]
Artes, Marta H. [1 ]
Llop, Sandra [2 ]
Penin, Rosa M. [3 ]
Bermejo, Josep Oriol [4 ]
Gonzalez-Suarez, Eva [1 ,5 ]
Esteller, Manel [6 ,7 ,8 ,9 ]
Vinals, Francesc [1 ,9 ,10 ]
Espinosa, Enrique [7 ,11 ]
Oliva, Marc [2 ]
Piulats, Josep M. [1 ,2 ]
Martin-Liberal, Juan [2 ]
Munoz, Purificacion [1 ]
机构
[1] Bellvitge Biomed Res Inst IDIBELL, Oncobell Program, Lhospitalet De Llobregat 08908, Barcelona, Spain
[2] Catalan Inst Oncol ICO, Med Oncol Dept, Lhospitalet De Llobregat 08908, Barcelona, Spain
[3] Bellvitge Univ Hosp, Pathol Serv, IDIBELL, Lhospitalet De Llobregat 08908, Barcelona, Spain
[4] Bellvitge Univ Hosp, Plast Surg Unit, IDIBELL, Lhospitalet De Llobregat 08908, Barcelona, Spain
[5] Spanish Natl Canc Res Ctr CNIO, Mol Oncol, Madrid 28029, Spain
[6] Josep Carreras Leukaemia Res Inst IJC, Badalona 08916, Barcelona, Spain
[7] ISCIII, Ctr Invest Biomed Red Canc CIBERONC, Madrid 28029, Spain
[8] Inst Catalana Recerca & Estudis Avancats ICREA, Barcelona 08010, Spain
[9] Univ Barcelona UB, Sch Med & Hlth Sci, Physiol Sci Dept, Barcelona 08908, Spain
[10] IDIBELL, Catalan Inst Oncol ICO, Program Canc Therapeut Resistance ProCURE, Lhospitalet De Llobregat 08908, Barcelona, Spain
[11] Autonomous Univ Madrid UAM, La Paz Univ Hosp, Med Oncol Dept, Madrid 28046, Spain
[12] Rutgers State Univ, Rutgers Canc Inst New Jersey, New Brunswick, NJ 08901 USA
关键词
EPITHELIAL-MESENCHYMAL TRANSITION; OPEN-LABEL; ACQUIRED-RESISTANCE; IMMUNE CHECKPOINTS; SIGNALING PATHWAYS; NIVOLUMAB; METASTASIS; LANDSCAPE; STATES; HEAD;
D O I
10.1038/s41467-024-49718-8
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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. Immune surveillance is critical to prevent the development and progression of cutaneous squamous cell carcinoma (cSCC). Here, the authors show that epithelial-mesenchymal plasticity in cancer cells is associated with changes in their immune checkpoint ligand profile during mouse cSCC progression, which dictates differential responses to immune checkpoint blockade.
引用
收藏
页数:18
相关论文
共 104 条
[1]   Interplay between tumor microenvironment and partial EMT as the driver of tumor progression [J].
Aggarwal, Vaishali ;
Montoya, Catalina Ardila ;
Donnenberg, Vera S. ;
Sant, Shilpa .
ISCIENCE, 2021, 24 (02)
[2]   EMT Subtype Influences Epithelial Plasticity and Mode of Cell Migration [J].
Aiello, Nicole M. ;
Maddipati, Ravikanth ;
Norgard, Robert J. ;
Balli, David ;
Li, Jinyang ;
Yuan, Salina ;
Yamazoe, Taiji ;
Black, Taylor ;
Sahmoud, Amine ;
Furth, Emma E. ;
Bar-Sagi, Dafna ;
Stanger, Ben Z. .
DEVELOPMENTAL CELL, 2018, 45 (06) :681-+
[3]   Lag-3, Tim-3, and TIGIT: Co-inhibitory Receptors with Specialized Functions in Immune Regulation [J].
Anderson, Ana C. ;
Joller, Nicole ;
Kuchroo, Vijay K. .
IMMUNITY, 2016, 44 (05) :989-1004
[4]   Cancer cell states recur across tumor types and form specific interactions with the tumor microenvironment [J].
Barkley, Dalia ;
Moncada, Reuben ;
Pour, Maayan ;
Liberman, Deborah A. ;
Dryg, Ian ;
Werba, Gregor ;
Wang, Wei ;
Baron, Maayan ;
Rao, Anjali ;
Xia, Bo ;
Franca, Gustavo S. ;
Weil, Alejandro ;
Delair, Deborah F. ;
Hajdu, Cristina ;
Lund, Amanda W. ;
Osman, Iman ;
Yanai, Itai .
NATURE GENETICS, 2022, 54 (08) :1192-+
[5]   Epithelial-mesenchymal transition during invasion of cutaneous squamous cell carcinoma is paralleled by AKT activation [J].
Barrette, K. ;
Van Kelst, S. ;
Wouters, J. ;
Marasigan, V. ;
Fieuws, S. ;
Agostinis, P. ;
van den Oord, J. ;
Garmyn, M. .
BRITISH JOURNAL OF DERMATOLOGY, 2014, 171 (05) :1014-1021
[6]   Therapeutic Targeting of the Tumor Microenvironment [J].
Bejarano, Leire ;
Jordao, Marta J. C. ;
Joyce, Johanna A. .
CANCER DISCOVERY, 2021, 11 (04) :933-959
[7]   FGFR Inhibition Overcomes Resistance to EGFR-targeted Therapy in Epithelial-like Cutaneous Carcinoma [J].
Bernat-Peguera, Adria ;
Navarro-Ventura, Juan ;
Lorenzo-Sanz, Laura ;
da Silva-Diz, Victoria ;
Bosio, Mattia ;
Palomero, Luis ;
Penin, Rosa M. ;
Perez Sidelnikova, Diana ;
Oriol Bermejo, Josep ;
Taberna, Miren ;
Vilarino, Noelia ;
Piulats, Josep M. ;
Mesia, Ricard ;
Maria Vinals, Joan ;
Gonzalez-Suarez, Eva ;
Capella-Gutierrez, Salvador ;
Villanueva, Alberto ;
Vinals, Francesc ;
Munoz, Purificacion .
CLINICAL CANCER RESEARCH, 2021, 27 (05) :1491-1504
[8]   PDGFR-induced autocrine SDF-1 signaling in cancer cells promotes metastasis in advanced skin carcinoma [J].
Bernat-Peguera, Adria ;
Simon-Extremera, Pilar ;
da Silva-Diz, Victoria ;
Lopez de Munain, Mikel ;
Diaz-Gil, Laura ;
Penin, Rosa M. ;
Gonzalez-Suarez, Eva ;
Sidelnikova, Diana Perez ;
Bermejo, Oriol ;
Vinals, Joan Maria ;
Vinals, Francesc ;
Munoz, Purificacion .
ONCOGENE, 2019, 38 (25) :5021-5037
[9]   Cytokines in clinical cancer immunotherapy [J].
Berraondo, Pedro ;
Sanmamed, Miguel F. ;
Ochoa, Maria C. ;
Etxeberria, Inaki ;
Aznar, Maria A. ;
Luis Perez-Gracia, Jose ;
Rodriguez-Ruiz, Maria E. ;
Ponz-Sarvise, Mariano ;
Castanon, Eduardo ;
Melero, Ignacio .
BRITISH JOURNAL OF CANCER, 2019, 120 (01) :6-15
[10]   Interrogation of Phenotypic Plasticity between Epithelial and Mesenchymal States in Breast Cancer [J].
Bhatia, Sugandha ;
Monkman, James ;
Blick, Tony ;
Pinto, Cletus ;
Waltham, Mark ;
Nagaraj, Shivashankar H. ;
Thompson, Erik W. .
JOURNAL OF CLINICAL MEDICINE, 2019, 8 (06)