Immunotherapy for Uveal Melanoma

Kim, Dae Won; Anderson, Joshua P.; Patel, Sapna

doi:10.2217/mmt-2015-0006

Cited by 4 publications

(3 citation statements)

References 91 publications

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“…Immune checkpoint inhibitor therapies, such as PD-1/PDL-1 or CTLA-4 inhibitors, that have made breakthroughs in the treatment of other solid tumors with a high mutation load, are being investigated for their utility in UVM ( 9 ). However, at present, a large number of UVM patients do not respond well to immune checkpoint inhibitors, which may be related to low mutation load, new immune checkpoint acquisition, and the production of immunosuppressive factors ( 10 ). Therefore, it is necessary to explore novel biomarkers of UVM and understand their significance in the tumor microenvironment.…”

Section: Introductionmentioning

confidence: 99%

A Necroptosis-Related Prognostic Model of Uveal Melanoma Was Constructed by Single-Cell Sequencing Analysis and Weighted Co-Expression Network Analysis Based on Public Databases

et al. 2022

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BackgroundUveal melanoma(UVM) is the most common intraocular malignancy and has a poor prognosis. The clinical significance of necroptosis(NCPS) in UVM is unclear.MethodsWe first identified necroptosis genes in UVM by single-cell analysis of the GSE139829 dataset from the GEO database and weighted co-expression network analysis of TCGA data. COX regression and Lasso regression were used to construct the prognostic model. Then survival analysis, immune microenvironment analysis, and mutation analysis were carried out. Finally, cell experiments were performed to verify the role of ITPA in UVM.ResultBy necroptosis-related prognostic model, UVM patients in both TCGA and GEO cohorts could be classified as high-NCPS and low-NCPS groups, with significant differences in survival time between the two groups (P<0.001). Besides, the high-NCPS group had higher levels of immune checkpoint-related gene expression, suggesting that they might be more likely to benefit from immunotherapy. The cell experiments confirmed the role of ITPA, the most significant gene in the model, in UVM. After ITPA was knocked down, the activity, proliferation, and invasion ability of the MuM-2B cell line were significantly reduced.ConclusionOur study can provide a reference for the diagnosis and treatment of patients with UVM.

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Section: Introductionmentioning

confidence: 99%

A Necroptosis-Related Prognostic Model of Uveal Melanoma Was Constructed by Single-Cell Sequencing Analysis and Weighted Co-Expression Network Analysis Based on Public Databases

et al. 2022

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“…Некоторые исследователи [38,39] полагают, что УМ «ускользает» от воздействия иммунной системы организма. Однако, несмотря на выраженную иммуносупрессивную активность клеток УМ, имеющееся лимфоцитарное микроокружение, несомненно, оказывает воздействие на опухоль, что может явиться обоснованием к иммунотерапевтическому подходу в лечении данного новообразования.…”

Section: Discussionunclassified

Cellular and stromal microenvironment of metastatic choroidal melanoma

Kazachkov¹,

Shamanova²,

Панова³

et al. 2021

Clin. Exp. Morphology

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Introduction. Choroidal melanoma is a malignant neoplasm of the eye’s vascular membrane. Prognosing and preventing metastasis are the main objectives of ocular oncology, aimed at maximizing the relapse-free survival of patients. Our goal was to determine the features of the cellular and stromal microenvironment of metastatic choroidal melanoma based on the immunohistochemical characteristics of surgical specimens. Materials and methods. We conducted a retrospective analysis of surgical specimens of cases of choroidal melanoma obtained from 2013 to 2017 and divided them into 2 study groups: group 1 included cases of choroidal melanoma without distant metastases (n=25) and group 2 involved cases of choroidal melanoma with distant liver metastases (n=18). The study was conducted using medical records analysis, histological, immunohistochemical, morphometric, and statistical research methods. Results. In group 2, the level of cells expressing CD4 markers – 138.5 (99.8;153.3), CD68 – 137 (99,5;173,8) and CD56 [5 (3;6)] prevailed significantly. The indicators of CD4 lymphocytes >95 and CD68 macro-phages >104 were found to allow the prediction of the appearance of distant choroidal melanoma metastases with the sensitivity of 83.3% and 72.2% and specificity of 76% and 76%, respectively. The indicators of the volume density of blood vessels in the tumor <3.9 (with a sensitivity of 77.8% and specificity of 64%) were of the same prognostic value. Conclusion. Metastatic choroidal melanoma is characterized by features of the cellular and stromal microen-vironment. Quantitative indicators of CD4 lymphocytes and CD68-macrophages and the volume density of blood vessels in the tumor have prognostic value with high sensitivity and specificity for predicting distant tumor metastasis. Keywords: choroidal melanoma, lymphocytes, macrophages, metastases, tumor blood vessels

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“…Возможная точка воздействия при данном варианте терапии -блокада взаимодействия между рецептором цитотоксического лимфоцита PD-1 и опухолевым лигандом PD-L1, что, в свою очередь, приводит к активации иммунной системы в ее противоопухолевому воздействию. Но доказанное иммуноподавляющее влияние УМ приводит к низкому содержанию иммунных клеток в опухоли (в первую очередь, лимфоцитов), что делает невозможным достижение успеха в применении иммунотерапии в силу «ускользания» УМ от воздействия иммунной системы организма [16][17][18][19][20]. L. A. Kottschade et al [21] были опубликованы результаты на выборке 10 пациентов с УМ IV стадии (с отдаленными метастазами), получавших терапию анти-PD1 (пембролизумаб), показавшие, что из 8 пациентов, подлежащих оценке, один полный ответ на терапию, два частичных ответа и один пациент со стабильным течением заболевания без прогрессирования (медиана выживаемости без прогрессирования составила 18 недель, диапазон -3,14-49,3 недели) [21].…”

Section: Introductionunclassified

Features of the lymphocytic microenvironment in metastatic uveal melanoma

Шаманова

Kazachkov

Панова

et al. 2021

jour

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Introduction. Uveal melanoma is a malignant neoplasm of the vascular tract of the eye. Prevention of metastasis of this tumor is one of the main tasks in order to increase the rates of relapse-free survival of patients. Despite the pronounced immunosuppressive activity of uveal melanoma cells, its lymphocytic microenvironment exerts its antitumor effect.Aim of the study. Compare the lymphocytic microenvironment of primary uveal melanomas and distant metastases (to the liver).Мaterials and methods. The tissue material of choroid melanoma after enucleation and the material of tumor metastases for the period 2013-2018 were studied. An immunohistochemical study was performed using CD8, CD4, and CD56 markers for the qualitative and quantitative assessment of lymphocytes in the tumor stroma.Results. Differences were found in the lymphocytic infiltration of the uveal melanoma stroma and its distant metastases. A statistically significantly greater representation of CD4, CD8-lymphocytes and CD56 cells in tumor metastases than in primary melanoma tissue samples, with CD4-lymphocytes predominant. A direct high-strength correlation was registered between the number of CD4-lymphocytes and CD8-lymphocytes.Discussion. Malignant cells actively modify their cellular and stromal-vascular environment, ensuring their active growth and reproduction. The question of the immune reactivity of the surrounding cells in relation to uveal melanoma remains debatable. According to our data, which is consistent with a number of other studies, uveal melanoma cells do not completely evade the body's immune response. Thus, the determination of possible points of antitumor exposure can be based on a detailed study of the microenvironment of uveal melanoma. Conclusions. The pronounced lymphocytic infiltrate found in uveal melanoma metastases in comparison with the primary tumor indicates an active immune response of the body to the tumor. These results of our study confirm the importance of further studying the immune-mediated antitumor effect on uveal melanoma and the need to investigate possible approaches to immunotherapy.

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Immunotherapy for Uveal Melanoma

Cited by 4 publications

References 91 publications

A Necroptosis-Related Prognostic Model of Uveal Melanoma Was Constructed by Single-Cell Sequencing Analysis and Weighted Co-Expression Network Analysis Based on Public Databases

A Necroptosis-Related Prognostic Model of Uveal Melanoma Was Constructed by Single-Cell Sequencing Analysis and Weighted Co-Expression Network Analysis Based on Public Databases

Cellular and stromal microenvironment of metastatic choroidal melanoma

Features of the lymphocytic microenvironment in metastatic uveal melanoma

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