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

Cancer Immunology, Immunotherapy : CII
Andreas WielandRafi Ahmed

Abstract

PD-1-targeted therapy has dramatically changed advanced cancer treatment. However, many questions remain, including specificity of T cells activated by PD-1 therapy and how peripheral blood analysis correlates to effects at tumor sites. 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 peripheral 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 present at low frequencies in the peripheral blood but were enriched in a previously resected liver metastasis. The patient has so far remained re...Continue Reading

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Citations

Dec 7, 2019·Immunological Reviews·Christina R HartiganMandy L Ford
May 21, 2020·Frontiers in Immunology·Silvia PiconeseAmbra Natalini
Aug 12, 2020·Clinical and Translational Medicine·Che-Mai ChangYun Yen
Sep 9, 2020·Nature Biotechnology·Pierre BarennesEncarnita Mariotti-Ferrandiz
Feb 9, 2020·Proceedings of the National Academy of Sciences of the United States of America·Se Jin ImRafi Ahmed
Jun 20, 2020·Journal of Leukocyte Biology·Sohini RoyDouglas B Johnson
Apr 9, 2020·Frontiers in Immunology·Lara GibelliniAndrea Cossarizza
Jan 6, 2019·Nature Reviews. Drug Discovery·Jérôme Galon, Daniela Bruni
Dec 5, 2019·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·Guoliang QiaoHerbert Kim Lyerly
Nov 15, 2020·Journal for Immunotherapy of Cancer·Sylvain SimonNathalie Labarriere
Mar 17, 2021·Nature Communications·Sara De BiasiAndrea Cossarizza
Mar 19, 2021·Frontiers in Immunology·Kim M van PulTanja D de Gruijl
Jun 8, 2021·Frontiers in Oncology·Mara De MartinoClaire Vanpouille-Box
Jul 30, 2021·Frontiers in Immunology·Daniel BodeDavid G Kent
Sep 3, 2021·Nature·Christiane S EberhardtRafi Ahmed

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