tetano
Editor, Senior Moderator
Front Immunol
. 2024 Aug 27:15:1447555.
doi: 10.3389/fimmu.2024.1447555. eCollection 2024. mRNA-1273 vaccination induces polyfunctional memory CD4 and CD8 T cell responses in patients with solid cancers undergoing immunotherapy or/and chemotherapy
Anastasia Gangaev[SUP] 1 [/SUP], Yannick van Sleen[SUP] 2 [/SUP], Nicole Brandhorst[SUP] 1 [/SUP], Kelly Hoefakker[SUP] 1 [/SUP], Bimal Prajapati[SUP] 2 [/SUP], Amrita Singh[SUP] 2 [/SUP], Annemarie Boerma[SUP] 2 [/SUP], Marieke van der Heiden[SUP] 2 [/SUP], Sjoukje F Oosting[SUP] 3 [/SUP], Astrid A M van der Veldt[SUP] 4 [/SUP], T Jeroen N Hiltermann[SUP] 5 [/SUP], Corine H GeurtsvanKessel[SUP] 6 [/SUP], Anne-Marie C Dingemans[SUP] 7 [/SUP], Egbert F Smit[SUP] 8 [/SUP], Elisabeth G E de Vries[SUP] 3 [/SUP], John B A G Haanen[SUP] 1 [/SUP], Pia Kvistborg[SUP] 1 [/SUP], Debbie van Baarle[SUP] 2 9 [/SUP]
Affiliations
Introduction: Research has confirmed the safety and comparable seroconversion rates following SARS-CoV-2 vaccination in patients with solid cancers. However, the impact of cancer treatment on vaccine-induced T cell responses remains poorly understood.
Methods: In this study, we expand on previous findings within the VOICE trial by evaluating the functional and phenotypic composition of mRNA-1273-induced T cell responses in patients with solid tumors undergoing immunotherapy, chemotherapy, or both, compared to individuals without cancer. We conducted an ELISpot analysis on 386 participants to assess spike-specific T cell responses 28 days after full vaccination. Further in-depth characterization of using flow cytometry was performed on a subset of 63 participants to analyze the functional phenotype and differentiation state of spike-specific T cell responses.
Results: ELISpot analysis showed robust induction of spike-specific T cell responses across all treatment groups, with response rates ranging from 75% to 80%. Flow cytometry analysis revealed a distinctive cytokine production pattern across cohorts, with CD4 T cells producing IFNγ, TNF, and IL-2, and CD8 T cells producing IFNγ, TNF, and CCL4. Variations were observed in the proportion of monofunctional CD4 T cells producing TNF, particularly higher in individuals without cancer and patients treated with chemotherapy alone, while those treated with immunotherapy or chemoimmunotherapy predominantly produced IFNγ. Despite these differences, polyfunctional spike-specific memory CD4 and CD8 T cell responses were comparable across cohorts. Notably, immunotherapy-treated patients exhibited an expansion of spike-specific CD4 T cells with a terminally differentiated effector memory phenotype.
Discussion: These findings demonstrate that systemic treatment in patients with solid tumors does not compromise the quality of polyfunctional mRNA-1273-induced T cell responses. This underscores the importance of COVID-19 vaccination in patients with solid cancers undergoing systemic treatment.
Keywords: COVID-19; COVID-19 vaccination; SARS-CoV-2-specific T cells; cancer; chemoimmunotherapy; chemotherapy; immunotherapy.
. 2024 Aug 27:15:1447555.
doi: 10.3389/fimmu.2024.1447555. eCollection 2024. mRNA-1273 vaccination induces polyfunctional memory CD4 and CD8 T cell responses in patients with solid cancers undergoing immunotherapy or/and chemotherapy
Anastasia Gangaev[SUP] 1 [/SUP], Yannick van Sleen[SUP] 2 [/SUP], Nicole Brandhorst[SUP] 1 [/SUP], Kelly Hoefakker[SUP] 1 [/SUP], Bimal Prajapati[SUP] 2 [/SUP], Amrita Singh[SUP] 2 [/SUP], Annemarie Boerma[SUP] 2 [/SUP], Marieke van der Heiden[SUP] 2 [/SUP], Sjoukje F Oosting[SUP] 3 [/SUP], Astrid A M van der Veldt[SUP] 4 [/SUP], T Jeroen N Hiltermann[SUP] 5 [/SUP], Corine H GeurtsvanKessel[SUP] 6 [/SUP], Anne-Marie C Dingemans[SUP] 7 [/SUP], Egbert F Smit[SUP] 8 [/SUP], Elisabeth G E de Vries[SUP] 3 [/SUP], John B A G Haanen[SUP] 1 [/SUP], Pia Kvistborg[SUP] 1 [/SUP], Debbie van Baarle[SUP] 2 9 [/SUP]
Affiliations
- PMID: 39257577
- PMCID: PMC11385311
- DOI: 10.3389/fimmu.2024.1447555
Introduction: Research has confirmed the safety and comparable seroconversion rates following SARS-CoV-2 vaccination in patients with solid cancers. However, the impact of cancer treatment on vaccine-induced T cell responses remains poorly understood.
Methods: In this study, we expand on previous findings within the VOICE trial by evaluating the functional and phenotypic composition of mRNA-1273-induced T cell responses in patients with solid tumors undergoing immunotherapy, chemotherapy, or both, compared to individuals without cancer. We conducted an ELISpot analysis on 386 participants to assess spike-specific T cell responses 28 days after full vaccination. Further in-depth characterization of using flow cytometry was performed on a subset of 63 participants to analyze the functional phenotype and differentiation state of spike-specific T cell responses.
Results: ELISpot analysis showed robust induction of spike-specific T cell responses across all treatment groups, with response rates ranging from 75% to 80%. Flow cytometry analysis revealed a distinctive cytokine production pattern across cohorts, with CD4 T cells producing IFNγ, TNF, and IL-2, and CD8 T cells producing IFNγ, TNF, and CCL4. Variations were observed in the proportion of monofunctional CD4 T cells producing TNF, particularly higher in individuals without cancer and patients treated with chemotherapy alone, while those treated with immunotherapy or chemoimmunotherapy predominantly produced IFNγ. Despite these differences, polyfunctional spike-specific memory CD4 and CD8 T cell responses were comparable across cohorts. Notably, immunotherapy-treated patients exhibited an expansion of spike-specific CD4 T cells with a terminally differentiated effector memory phenotype.
Discussion: These findings demonstrate that systemic treatment in patients with solid tumors does not compromise the quality of polyfunctional mRNA-1273-induced T cell responses. This underscores the importance of COVID-19 vaccination in patients with solid cancers undergoing systemic treatment.
Keywords: COVID-19; COVID-19 vaccination; SARS-CoV-2-specific T cells; cancer; chemoimmunotherapy; chemotherapy; immunotherapy.