Coordinated humoral and cellular immune responses to COVID-19 vaccination in non-small cell lung cancer patients treated with immune checkpoint inhibitors.

INTRODUCTION

Patients with non-small cell lung cancer (NSCLC) faced an elevated risk for severe COVID-19 outcomes and were prioritized for early vaccination. However, immune responses to SARS-CoV-2 vaccines remain poorly characterized in this group, especially in patients receiving immune checkpoint inhibitor PD-1/PDL-1 (ICI) therapy.

MATERIALS AND

METHODS

In this prospective observational study, we evaluated humoral and cellular immune responses to COVID-19 vaccination in 20 NSCLC patients receiving ICI therapy and compared to responses in 38 controls. Patients received two doses of either BNT162b2 (Pfizer-BioNTech) or ChAdOx1-S (AstraZeneca) vaccines followed by a third dose of BNT162b2 while controls received three doses of BNT162b2. Serum IgG to the receptor-binding domain (RBD) of the spike protein and T-cell cytokine responses (IFN-γ, IL-2 and TNF) induced by spike peptide stimulation of whole blood were assessed at multiple time points.

RESULTS AND DISCUSSION: After two doses, patients exhibited lower and more variable IgG responses than controls, but a third dose raised antibody levels to match those observed in controls. The largest fold-increase in antibody concentrations after the third dose occurred in patients receiving BNT162b2 after two doses of ChAdOx1-S. T-cell responses were significantly lower in patients after two doses but improved following the third dose. Antibody and IFN-γ responses were significantly correlated both after the second and third doses in patients, suggesting coordinated humoral and cellular immunity. No associations were found between immune responses and patient age. These findings highlight the immunogenicity of COVID-19 vaccines in NSCLC patients on ICI therapy and support that booster vaccinations are needed to enhance immunity in this vulnerable group.