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Peripheral T cell expansion predicts tumour infiltration and clinical response.
- Source :
-
Nature [Nature] 2020 Mar; Vol. 579 (7798), pp. 274-278. Date of Electronic Publication: 2020 Feb 26. - Publication Year :
- 2020
-
Abstract
- Despite the resounding clinical success in cancer treatment of antibodies that block the interaction of PD1 with its ligand PDL1 <superscript>1</superscript> , the mechanisms involved remain unknown. A major limitation to understanding the origin and fate of T cells in tumour immunity is the lack of quantitative information on the distribution of individual clonotypes of T cells in patients with cancer. Here, by performing deep single-cell sequencing of RNA and T cell receptors in patients with different types of cancer, we survey the profiles of various populations of T cells and T cell receptors in tumours, normal adjacent tissue, and peripheral blood. We find clear evidence of clonotypic expansion of effector-like T cells not only within the tumour but also in normal adjacent tissue. Patients with gene signatures of such clonotypic expansion respond best to anti-PDL1 therapy. Notably, expanded clonotypes found in the tumour and normal adjacent tissue can also typically be detected in peripheral blood, which suggests a convenient approach to patient identification. Analyses of our data together with several external datasets suggest that intratumoural T cells, especially in responsive patients, are replenished with fresh, non-exhausted replacement cells from sites outside the tumour, suggesting continued activity of the cancer immunity cycle in these patients, the acceleration of which may be associated with clinical response.
- Subjects :
- Antibodies, Monoclonal, Humanized therapeutic use
Antineoplastic Agents therapeutic use
Clone Cells
Humans
Neoplasms drug therapy
Neoplasms immunology
T-Lymphocytes metabolism
Transcriptome
Lymphocytes, Tumor-Infiltrating cytology
Lymphocytes, Tumor-Infiltrating metabolism
Neoplasms pathology
Pharmacogenomic Variants
Receptors, Antigen, T-Cell genetics
T-Lymphocytes cytology
Subjects
Details
- Language :
- English
- ISSN :
- 1476-4687
- Volume :
- 579
- Issue :
- 7798
- Database :
- MEDLINE
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 32103181
- Full Text :
- https://doi.org/10.1038/s41586-020-2056-8