Immune checkpoint inhibitors increase T cell immunity during SARS-CoV-2 infection

Nader Yatim (1, 2, 3) , Jeremy Boussier (4, 3) , Pauline Tetu (2, 3) , Nikaïa Smith (1) , Timothée Bruel (5) , Bruno Charbit (6) , Laura Barnabei (7) , Aurélien Corneau (8) , Laetitia da Meda (2, 3) , Clara Allayous (2, 3) , Barouyr Baroudjian (2, 3) , Majdi Jebali (2, 3) , Florian Herms (2, 3) , Ludivine Grzelak (5) , Isabelle Staropoli (5) , Vincent Calmettes (9, 10) , Jerome Hadjadj (7, 9, 10) , Olivier Peyrony (3) , Charles Cassius (2, 3) , Jerome Legoff (2, 3) , Nora Kramkimel (9, 10) , Selim Aractingi (9, 10) , Magnus Fontes (11) , Catherine Blanc (8) , Frederic Rieux-Laucat (7) , Olivier Schwartz (5, 12) , Benjamin Terrier (9, 10) , Darragh Duffy (1, 6) , Celeste Lebbé (2, 3)

1 Immunologie Translationnelle - Translational Immunology lab
2 HIPI (UMR_S_976 / U976) - Immunologie humaine, physiopathologie & immunothérapie
3 AP-HP - Hopital Saint-Louis [AP-HP]
4 SU - Sorbonne Université
5 CNRS-UMR3569 - Virus et Immunité - Virus and immunity
6 UTechS CB - Cytometrie et Biomarqueurs – Cytometry and Biomarkers
7 Equipe Inserm U1163 - Immunogenetics of pediatric autoimmune diseases
8 PASS-CYPS - Cytométrie Pitié-Salpêtrière
9 UPCité - Université Paris Cité
10 Hôpital Cochin [AP-HP]
11 Laboratoire Roche [Boulogne-Billancourt]
12 VRI - Vaccine Research Institute

The COVID-19 pandemic has spread worldwide, yet the role of antiviral T cell immunity during infection and the contribution of immune checkpoints remain unclear. By prospectively following a cohort of 292 patients with melanoma, half of which treated with immune checkpoint inhibitors (ICIs), we identified 15 patients with acute or convalescent COVID-19 and investigated their transcriptomic, proteomic, and cellular profiles. We found that ICI treatment was not associated with severe COVID-19 and did not alter the induction of inflammatory and type I interferon responses. In-depth phenotyping demonstrated expansion of CD8 effector memory T cells, enhanced T cell activation, and impaired plasmablast induction in ICI-treated COVID-19 patients. The evaluation of specific adaptive immunity in convalescent patients showed higher spike (S), nucleoprotein (N), and membrane (M) antigen-specific T cell responses and similar induction of spike-specific antibody responses. Our findings provide evidence that ICI during COVID-19 enhanced T cell immunity without exacerbating inflammation.

Domains: Life Sciences [q-bio]; Immunology

Nader Yatim, Jeremy Boussier, Pauline Tetu, Nikaïa Smith, Timothée Bruel, et al.. Immune checkpoint inhibitors increase T cell immunity during SARS-CoV-2 infection. Science Advances , 2021, 7 (34), pp.eabg4081. ⟨10.1126/sciadv.abg4081⟩. ⟨pasteur-03334080⟩