Pre-vaccination transcriptomic profiles of immune responders to the MUC1 peptide vaccine for colon cancer prevention.

Autor:	Cameron CM; Department of Nutrition, Case Western Reserve University, Cleveland, OH, United States., Raghu V; Department of Computer Science, University of Pittsburgh, Pittsburgh, PA, United States.; Massachusetts General Hospital, Harvard Medical School, Cambridge, MA, United States., Richardson B; Department of Nutrition, Case Western Reserve University, Cleveland, OH, United States.; Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, United States., Zagore LL; Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, United States., Tamilselvan B; Department of Nutrition, Case Western Reserve University, Cleveland, OH, United States., Golden J; Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, United States., Cartwright M; Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, United States., Schoen RE; Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, Pittsburgh, PA, United States., Finn OJ; Department of Immunology, University of Pittsburgh, Pittsburgh, PA, United States., Benos PV; Department of Epidemiology, University of Florida, Gainesville, FL, United States.; Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA, United States., Cameron MJ; Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Oct 10; Vol. 15, pp. 1437391. Date of Electronic Publication: 2024 Oct 10 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1437391
Abstrakt:	Introduction: Self-antigens abnormally expressed on tumors, such as MUC1, have been targeted by therapeutic cancer vaccines. We recently assessed in two clinical trials in a preventative setting whether immunity induced with a MUC1 peptide vaccine could reduce high colon cancer risk in individuals with a history of premalignant colon adenomas. In both trials, there were immune responders and non-responders to the vaccine. Methods: Here we used PBMC pre-vaccination and 2 weeks after the first vaccine of responders and non-responders selected from both trials to identify early biomarkers of immune response involved in long-term memory generation and prevention of adenoma recurrence. We performed flow cytometry, phosflow, and differential gene expression analyses on PBMCs collected from MUC1 vaccine responders and non-responders pre-vaccination and two weeks after the first of three vaccine doses. Results: MUC1 vaccine responders had higher frequencies of CD4 cells pre-vaccination, increased expression of CD40L on CD8 and CD4 T-cells, and a greater increase in ICOS expression on CD8 T-cells. Differential gene expression analysis revealed that iCOSL, PI3K AKT MTOR, and B-cell signaling pathways are activated early in response to the MUC1 vaccine. We identified six specific transcripts involved in elevated antigen presentation, B-cell activation, and NF-κB1 activation that were directly linked to finding antibody response at week 12. Finally, a model using these transcripts was able to predict non-responders with accuracy. Discussion: These findings suggest that individuals who can be predicted to respond to the MUC1 vaccine, and potentially other vaccines, have greater readiness in all immune compartments to present and respond to antigens. Predictive biomarkers of MUC1 vaccine response may lead to more effective vaccines tailored to individuals with high risk for cancer but with varying immune fitness. Competing Interests: Author RS reports support from Freenome, Exact Sciences, and Immunovia during the conduct of the study. Author OF reports personal fees from PDS Biotech, Invectys, Immodulon, and Ardigen outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. (Copyright © 2024 Cameron, Raghu, Richardson, Zagore, Tamilselvan, Golden, Cartwright, Schoen, Finn, Benos and Cameron.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu