tetano
Editor, Senior Moderator
Hum Vaccin Immunother
. 2025 Dec;21(1):2599622.
doi: 10.1080/21645515.2025.2599622. Epub 2025 Dec 15. Pre-vaccine immune profiling in cancer patients identifies correlates of COVID-19 vaccine responses
Maryam Kazerani[SUP] 1 [/SUP], Simeon Mahov[SUP] 1 [/SUP], Joslyn Foley[SUP] 1 [/SUP], Noah M Merin[SUP] 1 [/SUP], So Yung Choi[SUP] 2 [/SUP], Joseph Lownik[SUP] 3 [/SUP], Alexander M Xu[SUP] 1 [/SUP], Larry Milshteyn[SUP] 1 [/SUP], Anton Luis Villamejor[SUP] 1 [/SUP], Maimoona Nadri[SUP] 4 [/SUP], Nathalie Nguyen[SUP] 4 [/SUP], Elham Kazemian[SUP] 4 [/SUP], Omid Hamid[SUP] 5 [/SUP], Justin Darrah[SUP] 1 [/SUP], Jun Gong[SUP] 4 [/SUP], Ronald Paquette[SUP] 1 [/SUP], Robert Vescio[SUP] 1 [/SUP], Inderjit Mehmi[SUP] 5 [/SUP], Warren G Tourtellotte[SUP] 6 [/SUP], V Krishnan Ramanujan[SUP] 3 [/SUP], Karen L Reckamp[SUP] 4 [/SUP], Jane C Figueiredo[SUP] 4 7 [/SUP], Akil Merchant[SUP] 1 [/SUP]
Affiliations
mRNA vaccines have been highly effective against SARS-CoV-2-related severe illness and are currently undergoing investigation as anti-cancer therapeutics. Our prior work has shown that patients undergoing cancer therapy have reduced immune responses to mRNA-based vaccines. Therefore, further investigation into immunologic responses in the setting of immune-altered hosts is warranted. In this study, we investigated pre-vaccination peripheral immune cell repertoire from a cohort of 66 patients with cancer on active treatment. Immune cell repertoire was characterized by mass cytometry to identify key immune subsets for COVID-19 vaccine response. Immunological populations were then assessed for their association with spike-specific antibody titers measured by ELISA and the breadth and depth of T-cell response to vaccine by TCR sequencing. Immune features significantly correlated with response were selected using an iterative bootstrapping model. We identified immunological features including abundance and functional state of T and B cells, expression of co-stimulatory and -inhibitory molecules, and presence of innate lymphoid cells, and myeloid-derived suppressor cells correlated with humoral and cellular responses. Our findings suggest that vaccine-induced immune responses could serve as biomarkers of immune fitness, in general and specifically for patients receiving anti-cancer mRNA vaccines, providing insights to tailor future therapeutic strategies for immune-altered patients.
Keywords: Immunophenotyping; SARS-CoV-2; TCR response; cancer; humoral response; immune fitness; vaccine.
. 2025 Dec;21(1):2599622.
doi: 10.1080/21645515.2025.2599622. Epub 2025 Dec 15. Pre-vaccine immune profiling in cancer patients identifies correlates of COVID-19 vaccine responses
Maryam Kazerani[SUP] 1 [/SUP], Simeon Mahov[SUP] 1 [/SUP], Joslyn Foley[SUP] 1 [/SUP], Noah M Merin[SUP] 1 [/SUP], So Yung Choi[SUP] 2 [/SUP], Joseph Lownik[SUP] 3 [/SUP], Alexander M Xu[SUP] 1 [/SUP], Larry Milshteyn[SUP] 1 [/SUP], Anton Luis Villamejor[SUP] 1 [/SUP], Maimoona Nadri[SUP] 4 [/SUP], Nathalie Nguyen[SUP] 4 [/SUP], Elham Kazemian[SUP] 4 [/SUP], Omid Hamid[SUP] 5 [/SUP], Justin Darrah[SUP] 1 [/SUP], Jun Gong[SUP] 4 [/SUP], Ronald Paquette[SUP] 1 [/SUP], Robert Vescio[SUP] 1 [/SUP], Inderjit Mehmi[SUP] 5 [/SUP], Warren G Tourtellotte[SUP] 6 [/SUP], V Krishnan Ramanujan[SUP] 3 [/SUP], Karen L Reckamp[SUP] 4 [/SUP], Jane C Figueiredo[SUP] 4 7 [/SUP], Akil Merchant[SUP] 1 [/SUP]
Affiliations
- PMID: 41399253
- PMCID: PMC12710909
- DOI: 10.1080/21645515.2025.2599622
mRNA vaccines have been highly effective against SARS-CoV-2-related severe illness and are currently undergoing investigation as anti-cancer therapeutics. Our prior work has shown that patients undergoing cancer therapy have reduced immune responses to mRNA-based vaccines. Therefore, further investigation into immunologic responses in the setting of immune-altered hosts is warranted. In this study, we investigated pre-vaccination peripheral immune cell repertoire from a cohort of 66 patients with cancer on active treatment. Immune cell repertoire was characterized by mass cytometry to identify key immune subsets for COVID-19 vaccine response. Immunological populations were then assessed for their association with spike-specific antibody titers measured by ELISA and the breadth and depth of T-cell response to vaccine by TCR sequencing. Immune features significantly correlated with response were selected using an iterative bootstrapping model. We identified immunological features including abundance and functional state of T and B cells, expression of co-stimulatory and -inhibitory molecules, and presence of innate lymphoid cells, and myeloid-derived suppressor cells correlated with humoral and cellular responses. Our findings suggest that vaccine-induced immune responses could serve as biomarkers of immune fitness, in general and specifically for patients receiving anti-cancer mRNA vaccines, providing insights to tailor future therapeutic strategies for immune-altered patients.
Keywords: Immunophenotyping; SARS-CoV-2; TCR response; cancer; humoral response; immune fitness; vaccine.