The The Prognostic Role of Cellular Models in Evaluating the Efficacy of Dendritic Cell Vaccines N.N. Petrov National Medical Research Center of Oncology, St. Petersburg, the Russian Federation

Nekhaeva, T. L., Danilova, A. B., Efremova, N. A., Danilov, A. O., Zuy, E. S., & Baldueva, I. A. (2026). The The Prognostic Role of Cellular Models in Evaluating the Efficacy of Dendritic Cell Vaccines N.N. Petrov National Medical Research Center of Oncology, St. Petersburg, the Russian Federation. Voprosy Onkologii, 72(2), OF–2501. https://doi.org/10.37469/0507-3758-2026-72-2-OF-2501

Abstract

Introduction. Anticancer vaccines based on activated dendritic cells (DCs) are of significant interest. Constructing and utilizing cellular models that reproduce immunological responses for monitoring such therapy and predicting disease outcomes is a promising approach.

Aim. To develop autologous cellular models that reproduce in vitro activation of antitumor mechanisms following exposure to a DC vaccine and to study their prognostic value during treatment.

Materials and Methods. Biological material was obtained from 11 patients (7 with skin melanoma, 4 with soft tissue or osteogenic sarcomas (STS/OS)) treated with the autologous CaTeVac vaccine in N.N. Petrov National Medical Research Center of Oncology. Cellular models were created using cultures of patient-derived tumor cells and T-lymphocytes activated via coculture with vaccine DCs. The models were analyzed using flow cytometry, enzyme-linked immunosorbent assay (ELISA), and assessment of tumor cell proliferation potential.

Results. Generation of activated T-lymphocytes in response to vaccine DC stimulation was observed in 90.9 % of patients prior to treatment. The modeled interaction between T-lymphocytes and autologous tumor cells reproduced the clinical response in in 8 out of 11 (72.7 %) of cases. Inverse correlations were found between the levels of MICA and TGFβ₁ secreted by tumor cells and the cell lysis ratio (rho = –0.792, p = 0.001 and rho = –0. 472, p = 0.048, respectively), and between relative content of proliferating CD3+CFSE+ lymphocytes and plasma concentrations of IL-10 (rho = -0.579, p = 0.019) and TGFβ₁(rho = –0,512, p = 0,043) in patients' peripheral blood before treatment.

During the formation of a proliferating CD3+ cell clone, an increase in the subset of terminally differentiated lymphocytes (TEMRA) CD4+ (p = 0.018) and CD8+ (p = 0.048) was observed in patients with a sufficient effect (SE) before treatment compared to those with an insufficient effect (IE). After 2–6 cycles of DCV, SE patients experienced a significant increase in the number of CD8+ effector memory cells (CD8+Tem) (p = 0.036) and TEMRA CD8+ lymphocytes producing granzyme B (TEMRA GrB+CD8+) (p = 0.025).

Conclusion. The cytotoxic properties of antigen-specific T-lymphocytes induced by mature DCs vary between patients and correlate with the clinical disease presentation and therapy response. This supports the use of 2D and 3D cellular modeling as an in vitro method for predicting and monitoring the efficacy of dendritic cell-based immunotherapy.

https://doi.org/10.37469/0507-3758-2026-72-2-OF-2501

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