Особенности дифференцировки и поляризации Т-хелперов периферической крови у пациентов с первичной меланомой кожи

Kisseleva, E. P., Kudryavtsev, I. V., Rubinstein, A. A., Starikova, E. A., Mammedova, J. T., Nekhaeva, T. L., Novik , A. V., & Baldueva, I. A. (2025). Altered Peripheral Blood T-Helper Cell Maturation and Polarization in Primary Skin Melanoma. Voprosy Onkologii, 71(4), OF–2436. https://doi.org/10.37469/0507-3758-2025-71-4-OF-2436

Abstract

Introduction. CD4+ T lymphocytes play a key role in immune regulation and are crucial for antitumor defense. They constitute a heterogeneous population that necessitates selective analysis of individual subsets.
Aim. To study the maturation and subset composition of peripheral blood CD4+ T lymphocytes in patients with inoperable cutaneous melanoma compared to healthy controls.
Materials and Methods. The study included 37 patients with disseminated or locally advanced unresectable cutaneous melanoma. Age- and sex-matched healthy donors were enrolled as controls. Multicolor flow cytometry was performed on peripheral blood samples to identify CD3+CD4+ lymphocyte subsets (Th): Th1, Th2, Th17, Tfh, as well as central memory (Th CM) and effector memory (Th EM) cells. Within the total EM and CM cell populations, we conducted detailed analysis of specific Th17 subsets ("classical" Th17, Th17.1, DN Th17 and DP Th17) and Tfh cell populations (Tfh1, Tfh2, Tfh17 and DP Tfh).
Results. While no quantitative changes were observed in the total pool of peripheral blood CD4+ T lymphocytes in cutaneous melanoma patients, we identified significant imbalances in specific subsets, including Th1/Th2 ratios among total CD4+ T lymphocytes, as well as within Th EM and Th CM populations. Furthermore, increased frequencies of memory Th CM and Th EM cells were detected. Shifts in the balance of individual Th17 EM and Tfh EM subsets were also observed. Disease severity correlated with several immunological parameters: elevated Th17 cell counts, decreased Tfh CM lymphocytes, altered ratios between memory cell subpopulations (naive Th and Th EM), and changes in Th17 CM subsets ("classical" Th17 and Th17.1). Collectively, these findings demonstrate an active immune response in melanoma patients involving both cellular immunity (Th1, Th2 and Th17 alterations) and humoral immunity (Tfh subset variations).
Conclusion. Analysis of individual CD4+ T lymphocyte subsets in peripheral blood from cutaneous melanoma patients provides more clinically relevant information than evaluation of the total heterogeneous cell population. Several of the identified parameters may serve as potential biomarkers for predicting disease outcomes or monitoring therapeutic efficacy

https://doi.org/10.37469/0507-3758-2025-71-4-OF-2436

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