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

• Published in: Journal for immunotherapy of cancer Vol. 12; no. 1; p. e007922
• Main Authors: Song, No-Joon, Chakravarthy, Karthik B, Jeon, Hyeongseon, Bolyard, Chelsea, Reynolds, Kelsi, Weller, Kevin P, Reisinger, Sarah, Wang, Yi, Li, Anqi, Jiang, Sizun, Ma, Qin, Barouch, Dan H, Rubinstein, Mark P, Shields, Peter G, Oltz, Eugene M, Chung, Dongjun, Li, Zihai
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd 04.01.2024; BMJ Publishing Group LTD; BMJ Publishing Group
• Series: Original research
• Subjects: Antibodies; Antigens; Cancer therapies; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cells; Clinical/Translational Cancer Immunotherapy; COVID-19; COVID-19 vaccines; Data analysis; Flow cytometry; Immunotherapy; Infections; Lung cancer; Lymphocytes; mRNA vaccines; Pandemics; Patients; Peptides; Severe acute respiratory syndrome coronavirus 2; Software; CD8-Positive T-Lymphocytes; COVID-19; CD4-Positive T-Lymphocytes
• ISSN: 2051-1426; 2051-1426
• DOI: 10.1136/jitc-2023-007922

BackgroundThe 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.MethodsWe 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.ResultsBooster 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.ConclusionWe 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.