The Polarity and Specificity of Antiviral T Lymphocyte Responses Determine Susceptibility to SARS-CoV-2 Infection in Patients with Cancer and Healthy Individuals - Archive ouverte HAL Access content directly
Journal Articles Cancer Discovery Year : 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
Imran Lahmar
  • Function : Author
Anne-Gaëlle Goubet
Yacine Haddad
  • Function : Author
Agathe Carrier
Marine Mazzenga
  • Function : Author
Damien Drubay
Carolina Alves Costa Silva
Eric de Sousa
Cassandra Thelemaque
  • Function : Author
Cléa Melenotte
  • Function : Author
Agathe Dubuisson
Arthur Geraud
  • Function : Author
Gladys Ferrere
Roxanne Birebent
Camille Bigenwald
  • Function : Author
Marion Picard
  • Function : Author
Luigi Cerbone
  • Function : Author
Joana Lérias
  • Function : Author
Ariane Laparra
Alice Bernard-Tessier
  • Function : Author
Benoît Kloeckner
  • Function : Author
Marianne Gazzano
  • Function : Author
François-Xavier Danlos
  • Function : Author
Safae Terrisse
  • Function : Author
Eugenie Pizzato
  • Function : Author
Caroline Flament
  • Function : Author
Pierre Ly
  • Function : Author
Eric Tartour
Nadine Benhamouda
  • Function : Author
Lydia Meziani
  • Function : Author
Abdelhakim Ahmed-Belkacem
Makoto Miyara
  • Function : Author
Guy Gorochov
Fabrice Barlesi
  • Function : Author
Alexandre Trubert
  • Function : Author
Benjamin Ungar
Yeriel Estrada
  • Function : Author
Caroline Pradon
  • Function : Author
Emmanuelle Gallois
  • Function : Author
Fanny Pommeret
  • Function : Author
Emeline Colomba
  • Function : Author
Pernelle Lavaud
Marc Deloger
Nathalie Droin
Eric Deutsch
Bertrand Gachot
  • Function : Author
Jean-Philippe Spano
  • Function : Author
Mansouria Merad
  • Function : Author
Florian Scotté
  • Function : Author
Aurélien Marabelle
Frank Griscelli
  • Function : Author
Jean-Yves Blay
Jean-Charles Soria
  • Function : Author
Miriam Merad
Fabrice André
Juliette Villemonteix
Mathieu Chevalier
Sophie Caillat-Zucman
Emma Guttman-Yassky
  • Function : Author
Odile Launay
Guido Kroemer
Markus Maeurer
Lisa Derosa

Abstract

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 and versions

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

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Cite

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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