Magnitude of antigen-specific T-cell immunity the month after completing vaccination series predicts the development of long-term persistence of antitumor immune response
Antigen-specific T-cell responses at baseline were associated with a 0.33-log increase in response at long-term follow-up, 95% CI (0.11, 0.54), p=0.003. 63% of patients that had HER2/neu specific T cells at baseline continued to have responses at long-term follow-up. Increased HER2/neu specific T-cell response 1 month after the vaccine series was associated with a 0.47-log increase in T-cell response at long-term follow-up, 95% CI (0.27, 0.67), p=2e-5. 74% of patients that had an increased IFN-γ HER2 response 1 month after vaccines retained immunity long-term. As the 1-month post-vaccination series precursor frequency of HER2+IFN-γ T-cell responses increased, the probability of retaining these responses long-term increased (OR=1.49 for every one natural log increase of precursor frequency, p=0.0002), reaching an OR of 20 for a precursor frequency of 1:3,000 CONCLUSIONS: Patients not destined to achieve long-term immunity can be identified immediately after completing the vaccine series. Log-fold increases in antigen-specific precursor frequencies after vaccinations correlate with increased odds of retaining long-term HER2 immune responses. Further vaccine boosting or immune checkpoint inhibitors or other immune stimulator therapy should be explored in patients that do not develop antigen-specific T-cell responses to improve overall response rates.
Authors
- Jong‐Baeck Lim (ORCID: https://orcid.org/0000-0003-0419-0422)
- James Y. Dai (ORCID: https://orcid.org/0000-0001-6479-9286)
- Jessica Reichow
- John B. Liao (ORCID: https://orcid.org/0000-0002-3018-7879)
- Sasha E. Stanton (ORCID: https://orcid.org/0000-0002-4300-551X)
- Katie M Hitchcock-Bernhardt (ORCID: https://orcid.org/0000-0003-1804-8507)
- Lupe G. Salazar (ORCID: https://orcid.org/0009-0003-8916-3024)
- Mary L. Disis
- Theodore A. Gooley
Institutions
- University of Washington (US)
- Providence Portland Medical Center (US)
- Fred Hutch Cancer Center (US)
Publication Details
- Journal
- Journal for ImmunoTherapy of Cancer
- Published
- 2024-11-01
- DOI
- https://doi.org/10.1136/jitc-2024-010251
- Primary Topic
- T-cell and B-cell Immunology
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- U.S. Department of Defense
- AstraZeneca
- University of Washington
- Aminex Therapeutics
- Bavarian Nordic
- National Institutes of Health
- Congressionally Directed Medical Research Programs
- Ovarian Cancer Academy