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Neoantigen-specific CD8 T cell responses in the peripheral blood following PD-L1 blockade might predict therapy outcome in metastatic urothelial carcinoma
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Neoantigen-specific CD8 T cell responses in the peripheral blood following PD-L1 blockade might predict therapy outcome in metastatic urothelial carcinoma
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Neoantigen-specific CD8 T cell responses in the peripheral blood following PD-L1 blockade might predict therapy outcome in metastatic urothelial carcinoma
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Journal Article
Neoantigen-specific CD8 T cell responses in the peripheral blood following PD-L1 blockade might predict therapy outcome in metastatic urothelial carcinoma
2022
Overview
CD8
+
T cell reactivity towards tumor mutation-derived neoantigens is widely believed to facilitate the antitumor immunity induced by immune checkpoint blockade (ICB). Here we show that broadening in the number of neoantigen-reactive CD8
+
T cell (NART) populations between pre-treatment to 3-weeks post-treatment distinguishes patients with controlled disease compared to patients with progressive disease in metastatic urothelial carcinoma (mUC) treated with PD-L1-blockade. The longitudinal analysis of peripheral CD8
+
T cell recognition of patient-specific neopeptide libraries consisting of DNA barcode-labelled pMHC multimers in a cohort of 24 patients from the clinical trial NCT02108652 also shows that peripheral NARTs derived from patients with disease control are characterised by a PD1
+
Ki67
+
effector phenotype and increased CD39 levels compared to bystander bulk- and virus-antigen reactive CD8
+
T cells. The study provides insights into NART characteristics following ICB and suggests that early-stage NART expansion and activation are associated with response to ICB in patients with mUC.
Immune checkpoint blockade therapy is successful in a high proportion of cancer patients, but others remain unresponsive. Authors here show that therapeutic success might be predictable in metastatic bladder cancer by longitudinal analysis of the early neoantigen-specific CD8 T cell response in peripheral blood.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 38/39
/ 38/91
/ Antigens
/ Blood
/ Cancer
/ Carcinoma, Transitional Cell - drug therapy
/ Carcinoma, Transitional Cell - genetics
/ Humanities and Social Sciences
/ Humans
/ Immune Checkpoint Inhibitors
/ Mutation
/ Patients
/ Science
/ Tumors
/ Urinary Bladder Neoplasms - drug therapy
