AUTHOR=Gangaev Anastasia , van Sleen Yannick , Brandhorst Nicole , Hoefakker Kelly , Prajapati Bimal , Singh Amrita , Boerma Annemarie , van der Heiden Marieke , Oosting Sjoukje F. , van der Veldt Astrid A. M. , Hiltermann T. Jeroen N. , GeurtsvanKessel Corine H. , Dingemans Anne-Marie C. , Smit Egbert F. , de Vries Elisabeth G. E. , Haanen John B. A. G. , Kvistborg Pia , van Baarle Debbie 

TITLE=mRNA-1273 vaccination induces polyfunctional memory CD4 and CD8 T cell responses in patients with solid cancers undergoing immunotherapy or/and chemotherapy

JOURNAL=Frontiers in Immunology

VOLUME=Volume 15 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1447555

DOI=10.3389/fimmu.2024.1447555

ISSN=1664-3224

ABSTRACT=Research has confirmed safety and comparable seroconversion rates after SARS-CoV-2 vaccination in patients with solid cancers. However, the impact of cancer treatment on vaccineinduced T cell responses remains poorly understood. In this study, we expand on previous findings within the VOICE trial, and evaluate the functional and phenotypic composition of mRNA-1273-induced T cell responses in patients with solid tumors undergoing immunotherapy, or/and chemotherapy, and individuals without cancer. ELISpot analysis of 386 participants showed a robust induction of spike-specific T cell responses 28 days after full vaccination irrespective of treatment with similar response rates ranging from 75% to 80%.Further in-depth characterization of identified spike-specific T cell responses using flow cytometry in a subset of 63 participants revealed a distinctive cytokine production pattern across all cohorts, with CD4 T cells producing IFNγ, TNF, and IL-2, while CD8 T cells produced IFNγ, TNF, and CCL4. Spike-specific CD4 T cells displayed cohort-specific variations characterized by a higher proportion of monofunctional cells producing TNF in individuals without cancer and patients treated with chemotherapy alone, whereas patients treated with immunotherapy alone or chemoimmunotherapy predominantly produced IFNγ.Nevertheless, polyfunctional spike-specific memory CD4 and CD8 T cell responses were comparable across cohorts. Interestingly, immunotherapy-treated patients exhibited expansion of spike-specific CD4 T cells with a terminally differentiated effector memory phenotype.Overall, these findings highlight that systemic treatment in patients with solid tumors does not compromise the quality of polyfunctional mRNA-1273-induced T cell responses, underscoring the importance of COVID-19 vaccination in patients with solid cancers undergoing systemic treatment.