DOI: https://doi.org/10.22263/2312-4156.2025.2.81
I.Y. Zherka, D.A. Davydov, E.P. Shupilova, A.F. Mahilyanchyk, A.S. Portyanko
Expression of immunosuppressive factors TGFβ1 and IDO1 in choroidal melanoma
N.N. Alexandrov National Cancer Centre of Belarus, Minsk, Republic of Belarus
Vestnik VGMU. 2025;24(2):81-91.
Abstract.
Objectives. To determine the prognostic value of IDO1 and TGFβ1 expression in relation to the course of choroidal melanoma.
Material and methods. In the retrospective study, we assessed the expression of IDO1 and TGFβ1 in tumor tissue samples from 64 patients with primary choroidal melanoma, for whom enucleation was the first treatment method. Regression analysis was used to assess the effect of potential risk factors on survival.
Results. The median follow-up was 86 (95% CI 38–120) months. Of the study cohort, the majority of tumors were TGFβ1-positive (79.6%) and IDO1-negative (85.9%). All IDO1-positive cases were also TGFβ1-positive. In the TGFβ1+ tumor group, signs of an unfavorable prognosis were statistically significantly more common: the presence of epithelioid cells in the tumor, the presence of vascular arches and loops, and the absence of nuclear expression of BAP. In addition, in case of TGFβ1+ expression, CD3-positive cells were statistically significantly less frequently detected in the tumor infiltrate, while the proportion of Foxp3-positive cells, on the contrary, was higher. In the IDO1+ group, earlier progression and death were observed compared to IDO1- tumors. The five-year overall survival in the IDO1+ group was 44.4±16.6%, in the IDO1- group – 72.6±6.3% (p=0.048).
Conclusions. Immunosuppressive microenvironment is associated with unfavorable course of choroidal melanoma. At the same time, most likely, increased expression of TGFβ1 itself does not contribute to a more aggressive course of the tumor process, but potentiates the activation of other mechanisms of immune suppression specific to the tumor. In particular, the unfavorable effect is realized due to hyperexpression of IDO1 in the choroidal melanoma tissues.
Keywords: choroidal melanoma, tumor microenvironment, prognosis, immunosuppressive tumor microenvironment.
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Submitted 14.10.2024
Accepted 14.04.2025
Information about authors:
Iryna Y. Zherka – Candidate of Medical Sciences, Senior Researcher of the Laboratory of Morphology, Molecular and Cellular Biology with Experimental Medicine Group, N.N. Alexandrov National Cancer Centre of Belarus, https://orcid.org/0000-0002-5134-3666, e-mail: Этот адрес электронной почты защищён от спам-ботов. У вас должен быть включен JavaScript для просмотра.;
D.A. Davydov – Candidate of Medical Sciences, Head of the Laboratory of Morphology, Molecular and Cellular Biology with Experimental Medicine Group, N.N. Alexandrov National Cancer Centre of Belarus;
E.P. Shupilova – Researcher of the Laboratory of Morphology, Molecular and Cellular Biology with Experimental Medicine Group, N.N. Alexandrov National Cancer Centre of Belarus;
A.F. Mahilyanchik – Junior Researcher of the Laboratory of Morphology, Molecular and Cellular Biology with Experimental Medicine Group, N.N. Alexandrov National Cancer Centre of Belarus;
A.S. Portyanko – Doctor of medical sciences, Head of the Republican Molecular Genetic Laboratory of Carcinogenesis, N.N. Alexandrov National Cancer Centre of Belarus.
