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Article Dans Une Revue Cancer Discovery Année : 2022

The Polarity and Specificity of Antiviral T Lymphocyte Responses Determine Susceptibility to SARS-CoV-2 Infection in Patients with Cancer and Healthy Individuals

Jean-Eudes Fahrner
Damien Drubay
Eric de Sousa
Joana Lérias
  • Fonction : Auteur
Eric Tartour
Abdelhakim Ahmed-Belkacem
Makoto Miyara
  • Fonction : Auteur
Guy Gorochov
Fabrice Barlesi
  • Fonction : Auteur
Alexandre Trubert
  • Fonction : Auteur
Benjamin Ungar
Yeriel Estrada
  • Fonction : Auteur
Caroline Pradon
  • Fonction : Auteur
Emmanuelle Gallois
  • Fonction : Auteur
Fanny Pommeret
  • Fonction : Auteur
Emeline Colomba
  • Fonction : Auteur
Pernelle Lavaud
Marc Deloger
Bertrand Gachot
  • Fonction : Auteur
Jean-Philippe Spano
Mansouria Merad
  • Fonction : Auteur
Florian Scotté
  • Fonction : Auteur
Aurélien Marabelle
Frank Griscelli
  • Fonction : Auteur
Jean-Yves Blay
Jean-Charles Soria
  • Fonction : Auteur
Miriam Merad
Juliette Villemonteix
Mathieu Chevalier
Sophie Caillat-Zucman
Emma Guttman-Yassky
  • Fonction : Auteur
Odile Launay
Markus Maeurer
Lisa Derosa

Résumé

Abstract Vaccination against coronavirus disease 2019 (COVID-19) relies on the in-depth understanding of protective immune responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We characterized the polarity and specificity of memory T cells directed against SARS-CoV-2 viral lysates and peptides to determine correlates with spontaneous, virus-elicited, or vaccine-induced protection against COVID-19 in disease-free and cancer-bearing individuals. A disbalance between type 1 and 2 cytokine release was associated with high susceptibility to COVID-19. Individuals susceptible to infection exhibited a specific deficit in the T helper 1/T cytotoxic 1 (Th1/Tc1) peptide repertoire affecting the receptor binding domain of the spike protein (S1-RBD), a hotspot of viral mutations. Current vaccines triggered Th1/Tc1 responses in only a fraction of all subject categories, more effectively against the original sequence of S1-RBD than that from viral variants. We speculate that the next generation of vaccines should elicit Th1/Tc1 T-cell responses against the S1-RBD domain of emerging viral variants. Significance: This study prospectively analyzed virus-specific T-cell correlates of protection against COVID-19 in healthy and cancer-bearing individuals. A disbalance between Th1/Th2 recall responses conferred susceptibility to COVID-19 in both populations, coinciding with selective defects in Th1 recognition of the receptor binding domain of spike. See related commentary by McGary and Vardhana, p. 892. This article is highlighted in the In This Issue feature, p. 873

Dates et versions

hal-03678977 , version 1 (25-05-2022)

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Citer

Jean-Eudes Fahrner, Imran Lahmar, Anne-Gaëlle Goubet, Yacine Haddad, Agathe Carrier, et al.. The Polarity and Specificity of Antiviral T Lymphocyte Responses Determine Susceptibility to SARS-CoV-2 Infection in Patients with Cancer and Healthy Individuals. Cancer Discovery, 2022, 12 (4), pp.958-983. ⟨10.1158/2159-8290.CD-21-1441⟩. ⟨hal-03678977⟩
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