Journal
EUROPEAN JOURNAL OF CANCER
Volume 162, Issue -, Pages 11-21Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.ejca.2021.11.015
Keywords
Immunotherapy; Immune-checkpoint blockade; Age; Melanoma; T cell receptor; T cell
Categories
Funding
- NIHR Manchester Biomedical Research Centre, CRUK [A27412, A22902]
- Harry J Lloyd Charitable Trust
- Wellcome Trust
- [100282/Z/12/Z]
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This study found that immunotherapy can induce changes in the clonality and diversity of the peripheral T cell receptor repertoire in patients with melanoma. Age has an impact on treatment response, with different age groups showing different response patterns.
Background: Precision immuno-oncology approaches are needed to improve cancer care. We recently demonstrated that in patients with metastatic melanoma, an increase of clonality or diversity of the T cell receptor (TCR) repertoire of peripheral T cells following one cycle of immunotherapy is coincident with response to immune-checkpoint blockade (ICB). We also identified a subset of peripheral CD8(+) immune-effector memory T cells (T-IE cells) whose expansion was associated with response to ICB and increased overall survival. To improve our understanding of peripheral T cell dynamics, we examined the clinical correlates associated with these immune signatures. Methods: Fifty patients with metastatic melanoma treated with first-line anti-PD-1 ICB were included. We analysed TCR repertoire and peripheral T-IE cell dynamics by age before treatment (T0) and after the first cycle of treatment at week 3 (W3). Results: We observed a correlation between T-IE abundance and age at T0 (r = 0.40), which reduced following treatment at W3 (r = 0.07). However, at W3, we observed two significantly opposing patterns (p = 0.03) of TCR repertoire rearrangement in patients who responded to treatment, with patients >= 70 years of age showing an increase in TCR clonality and patients < 70 years of age showing an increase in TCR diversity. Conclusions: We demonstrate that immunotherapy-induced immune-awakening patterns in patients with melanoma are age-related and may impact patient response to ICB, and thus have implications for biomarker development and planning of personalised therapeutic strategies. (c) 2021 The Authors. Published by Elsevier Ltd.
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