1. Clonally expanded EOMES+ Tr1-like cells in primary and metastatic tumors are associated with disease progression
- Author
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Salvatore Siena, Emilia Maria Cristina Mazza, Giulia Della Chiara, Chiara Godano, Nicola Zucchini, Valeria Ranzani, Stefania Oliveto, Paola Gruarin, Jens Geginat, Roberto Bosotti, Claudia D'Oria, Elena Carelli, Pierluigi Novellis, Saveria Mazzara, Ylenia Silvestri, Marco Passaro, Alessio Amatu, Marco Alloisio, Antonio Lanzavecchia, Stefano Biffo, Giorgia Alvisi, Federica Gervasoni, Maria Lucia Sarnicola, N. Mariani, Alberto Bardelli, Ramona Bason, Jolanda Brummelman, Mariangela Lorenzo, Giulia Veronesi, Emanuela Bonoldi, Massimiliano Pagani, Daniele Prati, Enrico Opocher, Lorenzo Drufuca, Martina Martinovic, Andrea Sartore-Bianchi, Sergio Abrignani, Alessandro Giani, Marco De Simone, Enrico Lugli, Chiara Cordiglieri, Serena Curti, Grazisa Rossetti, Valeria Bevilacqua, Andrea Pisani Ceretti, Raoul J. P. Bonnal, Bonnal, R. J. P., Rossetti, G., Lugli, E., De Simone, M., Gruarin, P., Brummelman, J., Drufuca, L., Passaro, M., Bason, R., Gervasoni, F., Della Chiara, G., D'Oria, C., Martinovic, M., Curti, S., Ranzani, V., Cordiglieri, C., Alvisi, G., Mazza, E. M. C., Oliveto, S., Silvestri, Y., Carelli, E., Mazzara, S., Bosotti, R., Sarnicola, M. L., Godano, C., Bevilacqua, V., Lorenzo, M., Siena, S., Bonoldi, E., Sartore-Bianchi, A., Amatu, A., Veronesi, G., Novellis, P., Alloisio, M., Giani, A., Zucchini, N., Opocher, E., Ceretti, A. P., Mariani, N., Biffo, S., Prati, D., Bardelli, A., Geginat, J., Lanzavecchia, A., Abrignani, S., and Pagani, M.
- Subjects
Male ,0301 basic medicine ,Lung Neoplasms ,T-Lymphocytes ,Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] ,medicine.medical_treatment ,Programmed Cell Death 1 Receptor ,Drug Resistance ,Datasets as Topic ,Kaplan-Meier Estimate ,Granzymes ,0302 clinical medicine ,Cancer immunotherapy ,Single-cell analysis ,80 and over ,Immunology and Allergy ,RNA-Seq ,Non-Small-Cell Lung ,Immune Checkpoint Inhibitors ,Adjuvant ,Colectomy ,Chitinases ,Cell Differentiation ,Forkhead Transcription Factors ,Middle Aged ,Flow Cytometry ,Regulatory ,Adult ,Aged ,Aged, 80 and over ,Carcinoma, Non-Small-Cell Lung ,Cell Proliferation ,Chemotherapy, Adjuvant ,Clonal Hematopoiesis ,Colon ,Colorectal Neoplasms ,Disease Progression ,Drug Resistance, Neoplasm ,Female ,Gene Expression Regulation, Neoplastic ,Humans ,Primary Cell Culture ,Single-Cell Analysis ,T-Box Domain Proteins ,T-Lymphocytes, Regulatory ,Immunology ,Biology ,03 medical and health sciences ,Immune system ,medicine ,Chemotherapy ,Neoplastic ,Carcinoma ,Immunotherapy ,030104 developmental biology ,Gene Expression Regulation ,Cell culture ,Cancer research ,Neoplasm ,Granzyme K ,Eomesodermin Homolog ,Checkpoint Blockade Immunotherapy ,030215 immunology - Abstract
Regulatory T (Treg) cells are a barrier for tumor immunity and a target for immunotherapy. Using single-cell transcriptomics, we found that CD4+ T cells infiltrating primary and metastatic colorectal cancer and non-small-cell lung cancer are highly enriched for two subsets of comparable size and suppressor function comprising forkhead box protein P3+ Treg and eomesodermin homolog (EOMES)+ type 1 regulatory T (Tr1)-like cells also expressing granzyme K and chitinase-3-like protein 2. EOMES+ Tr1-like cells, but not Treg cells, were clonally related to effector T cells and were clonally expanded in primary and metastatic tumors, which is consistent with their proliferation and differentiation in situ. Using chitinase-3-like protein 2 as a subset signature, we found that the EOMES+ Tr1-like subset correlates with disease progression but is also associated with response to programmed cell death protein 1–targeted immunotherapy. Collectively, these findings highlight the heterogeneity of Treg cells that accumulate in primary tumors and metastases and identify a new prospective target for cancer immunotherapy. Human primary and metastatic tumors harbor CD4+ Treg cells that can suppress antitumor immune responses. Bonnal et al. identify an intratumoral type 1 Treg-like CD4+ T cell subset that expresses the transcription factor EOMES, granzyme K and CHI3L2. This EOMES+ T cell subset correlates with disease progression but is responsive to PD-1 checkpoint blockade immunotherapy.
- Published
- 2021
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