mRNA vaccines against SARS-CoV-2 induce divergent antigen-specific T-cell responses in patients with lung cancer

Autor: Dan H Barouch, Yi Wang, Mark P Rubinstein, Zihai Li, Anqi Li, Sarah Reisinger, Peter G Shields, Qin Ma, No-Joon Song, Dongjun Chung, Karthik B Chakravarthy, Chelsea Bolyard, Hyeongseon Jeon, Kelsi Reynolds, Kevin P Weller, Sizun Jiang, Eugene M Oltz
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Journal for ImmunoTherapy of Cancer, Vol 12, Iss 1 (2024)
Druh dokumentu: article
ISSN: 2023-0079
2051-1426
DOI: 10.1136/jitc-2023-007922
Popis: Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant is highly transmissible and evades pre-established immunity. Messenger RNA (mRNA) vaccination against ancestral strain spike protein can induce intact T-cell immunity against the Omicron variant, but efficacy of booster vaccination in patients with late-stage lung cancer on immune-modulating agents including anti-programmed cell death protein 1(PD-1)/programmed death-ligand 1 (PD-L1) has not yet been elucidated.Methods We assessed T-cell responses using a modified activation-induced marker assay, coupled with high-dimension flow cytometry analyses. Peripheral blood mononuclear cells (PBMCs) were stimulated with various viral peptides and antigen-specific T-cell responses were evaluated using flow cytometry.Results Booster vaccines induced CD8+ T-cell response against the ancestral SARS-CoV-2 strain and Omicron variant in both non-cancer subjects and patients with lung cancer, but only a marginal induction was detected for CD4+ T cells. Importantly, antigen-specific T cells from patients with lung cancer showed distinct subpopulation dynamics with varying degrees of differentiation compared with non-cancer subjects, with evidence of dysfunction. Notably, female-biased T-cell responses were observed.Conclusion We conclude that patients with lung cancer on immunotherapy show a substantial qualitative deviation from non-cancer subjects in their T-cell response to mRNA vaccines, highlighting the need for heightened protective measures for patients with cancer to minimize the risk of breakthrough infection with the Omicron and other future variants.
Databáze: Directory of Open Access Journals
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