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Cancer Res. 2017 Dec 15;77(24):7083-7093. doi: 10.1158/0008-5472.CAN-17-1856. Epub 2017 Dec 6.

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

Simon S1,2, Vignard V1,2,3, Varey E4, Parrot T1,2, Knol AC1,2,4, Khammari A1,2,4, Gervois N1,2, Lang F1,2, Dreno B1,2,4, Labarriere N5,2,3.

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CRCINA, INSERM, Université d'Angers, Université de Nantes, Nantes, France.
LabEx IGO "Immunotherapy, Graft, Oncology," Nantes, France.
CHU Nantes, Nantes, France.
Department of Dermato-cancerology of Nantes Hospital, Nantes, France.
CRCINA, INSERM, Université d'Angers, Université de Nantes, Nantes, France.


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. Cancer Res; 77(24); 7083-93. ©2017 AACR.

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