T cell receptor sequencing of activated CD8 T cells in the blood identifies tumor-infiltrating clones that expand after PD-1 therapy and radiation in a melanoma patient

In this study, we utilized TCR sequencing to dissect the composition of peripheral blood CD8 T cells activated upon therapy, comparing it with tumor-infiltrating lymphocytes. We report on a nonagenarian melanoma patient who showed a prominent increase in peripheral blood Ki-67  + CD8 T cells following brain stereotactic radiation and anti-PD-1 immunotherapy. Proliferating CD8 T cells exhibited an effector-like phenotype with expression of CD38, HLA-DR and Granzyme B, as well as expression of the positive costimulatory molecules CD28 and CD27. TCR sequencing of periphe ral blood CD8 T cells revealed a highly oligoclonal repertoire at baseline with one clonotype accounting for 30%. However, the majority of dominant clones—including a previously identified cytomegalovirus-reactive clone—did not expand following treatment. In contrast, expanding clones were prese nt at low frequencies in the peripheral blood but were enriched in a previously resected liver metastasis. The patient has so far remained recurrence-free for 36 months, and several CD8 T cell clones that expanded after treatment were maintained at elevated levels for at least 8 months. Our data sho w that even in a nonagenarian individual with oligoclonal expansion of CD8 T cells, we can identify activation of tumor-infiltrating CD8 T cell clones in peripheral blood following anti-PD-1-based immunotherapies.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research

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Source: Journal of Photochemistry and Photobiology B: Biology - Category: Speech-Language Pathology Source Type: research
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Source: Journal of Genetics and Genomics - Category: Genetics & Stem Cells Source Type: research
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Source: Genetics and Molecular Biology - Category: Genetics & Stem Cells Source Type: research
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Source: European Urology Supplements - Category: Urology & Nephrology Source Type: research
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Source: European Urology Supplements - Category: Urology & Nephrology Source Type: research
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Source: Frontiers in cellular and infection microbiology - Category: Microbiology Source Type: research
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Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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