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Emergence of High-Avidity Melan-A–Specific Clonotypes as a Reflection of Anti–PD-1 Clinical Efficacy

Sylvain Simon 1, 2 Virginie Vignard 1, 2, 3 Emilie Varey 4 Tiphaine Parrot 1, 2 Anne-Chantal Knol 4, 5 Amir Khammari 4, 5 Nadine Gervois 1, 2 François Lang 1, 2 Brigitte Dreno 4, 5 Nathalie Labarrière 6, 2, *
* Corresponding author
1 CRCINA-ÉQUIPE 3 - Anti-Tumor Immunosurveillance and Immunotherapy
CRCINA - Centre de Recherche en Cancérologie et Immunologie Nantes-Angers
2 LabEX IGO Immunothérapie Grand Ouest
3 CHU Nantes - Centre hospitalier universitaire de Nantes
4 Département de Dermato-Cancerologie [CHU Nantes]
5 CRCINA-ÉQUIPE 2 - Clinical and Translational Research in Skin Cancer
CRCINA - Centre de Recherche en Cancérologie et Immunologie Nantes-Angers
6 CRCINA - Centre de Recherche en Cancérologie et Immunologie Nantes-Angers
Abstract : Therapeutic strategies using anti-PD-1-blocking antibodies reported unparalleled effectiveness for melanoma immunotherapy, but deciphering immune responses modulated by anti-PD-1 treatment remains a crucial issue. Here, we analyzed the composition and functions of the large Melan-A-specific T-cell repertoire in the peripheral blood of 9 melanoma patients before and after 2 months of treatment with anti-PD-1. We observed amplification of Melan-A-specific Vß subfamilies undetectable before therapy (thereafter called emerging Vß subfamilies) in responding patients, with a predominant expansion in patients with a complete response. These emerging Vß subfamilies displayed a higher functional avidity for their cognate antigen than Vß subfamilies not amplified upon anti-PD-1 therapy and could be identified by a sustained coexpression of PD-1 and TIGIT receptors. Thus, in addition to the emergence of neoantigen-specific T cells previously documented upon anti-PD-1 therapy, our work describes the emergence of high-avidity Melan-A-specific clonotypes as a surrogate marker of treatment efficacy.
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https://www.hal.inserm.fr/inserm-01636933
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Submitted on : Thursday, January 25, 2018 - 11:52:36 AM
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Sylvain Simon, Virginie Vignard, Emilie Varey, Tiphaine Parrot, Anne-Chantal Knol, et al.. Emergence of High-Avidity Melan-A–Specific Clonotypes as a Reflection of Anti–PD-1 Clinical Efficacy. Cancer Research, American Association for Cancer Research, 2017, 77 (24), pp.7083 - 7093. ⟨10.1158/0008-5472.CAN-17-1856⟩. ⟨inserm-01636933v2⟩

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