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

被引:30
作者
Yatim, Nader [1 ,2 ]
Boussier, Jeremy [3 ]
Tetu, Pauline [2 ]
Smith, Nikaia [1 ]
Bruel, Timothee [4 ,5 ]
Charbit, Bruno [6 ]
Barnabei, Laura [7 ]
Corneau, Aurelien [8 ]
Da Meda, Laetitia [2 ]
Allayous, Clara [2 ]
Baroudjian, Barouyr [2 ]
Jebali, Majdi [2 ]
Herms, Florian [2 ]
Grzelak, Ludivine [4 ]
Staropoli, Isabelle [4 ]
Calmettes, Vincent [9 ]
Hadjadj, Jerome [7 ,10 ]
Peyrony, Olivier [11 ]
Cassius, Charles [2 ]
LeGoff, Jerome [12 ]
Kramkimel, Nora [9 ]
Aractingi, Selim [9 ]
Fontes, Magnus [13 ]
Blanc, Catherine [8 ]
Rieux-Laucat, Frederic [7 ]
Schwartz, Olivier [4 ,5 ]
Terrier, Benjamin [10 ]
Duffy, Darragh [1 ,6 ]
Lebbe, Celeste [2 ]
机构
[1] Inst Pasteur, Dept Immunol, Translat Immunol Lab, F-75015 Paris, France
[2] Univ Paris, Hop St Louis, AP HP, DMU ICARE,INSERM U 976,Dermatol Dept, Paris, France
[3] Sorbonne Univ, Hop St Antoine, AP HP, F-75012 Paris, France
[4] CNRS, Inst Pasteur, Dept Virol, Virus & Immun Unit,UMR 3569, Paris, France
[5] Vaccine Res Inst, Creteil, France
[6] Inst Pasteur, Cytometry & Biomarkers UTechS, CRT, F-75015 Paris, France
[7] Univ Paris, INSERM, Lab Immunogenet Pediatr Autoimmune Dis, Imagine Inst,UMR 1163, F-75015 Paris, France
[8] Sorbonne Univ, Fac Med, Plateforme Cytometrie Pitie Salpetriere CyPS, PASS,UMS037, F-75013 Paris, France
[9] Univ Paris, Hop Cochin, AP HP, Dept Dermatol, Paris, France
[10] Univ Paris, Hop Cochin, AP HP, Ctr APHP CUP,Dept Internal Med,Natl Referral Ctr, F-75014 Paris, France
[11] Hop St Louis, AP HP, Emergency Dept, Paris, France
[12] Univ Paris, Hop St Louis, AP HP, Equipe INSIGHT,U976,Virol,INSERM, F-75010 Paris, France
[13] Inst Roche, Boulogne, France
关键词
COVID-19; CANCER; SEPSIS; SAFETY;
D O I
10.1126/sciadv.abg4081
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页数:13
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