Lineage tracing reveals clonal progenitors and long-term persistence of tumor-specific T cells during immune checkpoint blockade Journal Article
| Authors: | Pai, J. A.; Hellmann, M. D.; Sauter, J. L.; Mattar, M.; Rizvi, H.; Woo, H. J.; Shah, N.; Nguyen, E. M.; Uddin, F. Z.; Quintanal-Villalonga, A.; Chan, J. M.; Manoj, P.; Allaj, V.; Baine, M. K.; Bhanot, U. K.; Jain, M.; Linkov, I.; Meng, F.; Brown, D.; Chaft, J. E.; Plodkowski, A. J.; Gigoux, M.; Won, H. H.; Sen, T.; Wells, D. K.; Donoghue, M. T. A.; de Stanchina, E.; Wolchok, J. D.; Loomis, B.; Merghoub, T.; Rudin, C. M.; Chow, A.; Satpathy, A. T. |
| Article Title: | Lineage tracing reveals clonal progenitors and long-term persistence of tumor-specific T cells during immune checkpoint blockade |
| Abstract: | Paired single-cell RNA and T cell receptor sequencing (scRNA/TCR-seq) has allowed for enhanced resolution of clonal T cell dynamics in cancer. Here, we report a scRNA/TCR-seq analysis of 187,650 T cells from 31 tissue regions, including tumor, adjacent normal tissues, and lymph nodes (LN), from three patients with non-small cell lung cancer after immune checkpoint blockade (ICB). Regions with viable cancer cells are enriched for exhausted CD8+ T cells, regulatory CD4+ T cells (Treg), and follicular helper CD4+ T cells (TFH). Tracking T cell clonotypes across tissues, combined with neoantigen specificity assays, reveals that TFH and tumor-specific exhausted CD8+ T cells are clonally linked to TCF7+ SELL+ progenitors in tumor draining LNs, and progressive exhaustion trajectories of CD8+ T, Treg, and TFH cells with proximity to the tumor microenvironment. Finally, longitudinal tracking of tumor-specific CD8+ and CD4+ T cell clones reveals persistence in the peripheral blood for years after ICB therapy. © 2023 Elsevier Inc. |
| Keywords: | cd8+ t lymphocyte; cd8-positive t-lymphocytes; carcinoma, non-small-cell lung; lung neoplasms; lung cancer; lung tumor; receptors, antigen, t-cell; cell clone; clone cells; lymphocyte antigen receptor; non small cell lung cancer; tumor microenvironment; immune checkpoint blockade; humans; human; immune checkpoint inhibitors; exhausted t cells; single-cell rna/tcr sequencing; tcf-1 progenitor exhausted t cells; tumor-specific t cells |
| Journal Title: | Cancer Cell |
| Volume: | 41 |
| Issue: | 4 |
| ISSN: | 1535-6108 |
| Publisher: | Cell Press |
| Date Published: | 2023-04-10 |
| Start Page: | 776 |
| End Page: | 790.e7 |
| Language: | English |
| DOI: | 10.1016/j.ccell.2023.03.009 |
| PUBMED: | 37001526 |
| PROVIDER: | scopus |
| PMCID: | PMC10563767 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF. Corresponding author is MSK author Andrew Chow -- Source: Scopus |
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