Role of Natural Killer Cells in Uveal Melanoma

Javed, Asad; Milhem, Mohammed

doi:10.3390/cancers12123694

Cited by 20 publications

(18 citation statements)

References 171 publications

(258 reference statements)

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“…Вероятно, это связано с тем, что в строме УМ глаза скудно представлено воспалительное клеточное микроокружение. Глаз -это иммунопривилегированный орган, который хорошо защищен от возникновения местных воспалительных реакций через иммунологические барьеры с целью сохранения функциональной активности эндотелиальных клеток роговицы и сетчатки глаза, которые не склонны к регенерации [26,34]. Несмотря на это, по данным ряда авторов, наличие инфильтрирующих иммунных клеток при первичной увеальной меланоме является маркером плохого прогноза [35][36].…”

Section: Discussionunclassified

“…Представительство иммунных клеток в микроокружении опухоли количественно повышается, когда клетки меланомы выходят за пределы первичного очага (метастазируют в печень). Наши данные согласуются с результатами работ зарубежных исследователей [26]. Так, на примере натуральных киллеров авторами показано, что разнонаправленные противоопухолевые эффекторные реакций NK-клеток, которые не зависят от Т-лимфоцитов, могут быть использованы с целью поиска действенной терапии [26].…”

Section: Discussionunclassified

“…В публикации A. Javed et al (2020) [26] показано, что лимфоцитарное микроокружение клеток УМ стоит рассматривать в качестве потенциальных «защитников» от опухоли, и клетки микроокружения, в том числе натуральные киллеры, NK-клетки, особенно во вторичных очагах опухоли (метастазы в печени) могут рассматриваться как перспективные клетки для провоопухолевого воздействия [26]. Активно исследуется роль клеточного микроокружения при ЗНО различных локализаций, в том числе макрофагов [27][28].…”

Section: Introductionunclassified

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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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Section: Discussionunclassified

Section: Introductionunclassified

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Features of the lymphocytic microenvironment in metastatic uveal melanoma

Шаманова

Kazachkov

Панова

et al. 2021

jour

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“…The immune-suppressive microenvironment of the eye is assumed to generate a niche in which UM can grow and proliferate without the pressure of both innate and adaptive immune cells until it breaks the blood–retina barrier and disseminates. Innate cells, especially NK cells, are believed to be able to prevent metastases or to kill tumor cells in the blood before they could reach the liver [ 47 ]. However, after leaving the eye, the ability of UM cells to express pro-oncogenic molecules such as indoleamine dioxygenase-1 (IDO-1, [ 48 ]), MIF [ 49 ], and PD-L1 [ 50 ] enhance their metastatic potential.…”

Section: Immunobiology Of Uveal Melanomamentioning

confidence: 99%

How to Make Immunotherapy an Effective Therapeutic Choice for Uveal Melanoma

Marseglia

Amaro

Solari

et al. 2021

Cancers

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Uveal melanoma (UM), though a rare form of melanoma, is the most common intraocular tumor in adults. Conventional therapies of primary tumors lead to an excellent local control, but 50% of patients develop metastases, in most cases with lethal outcome. Somatic driver mutations that act on the MAP-kinase pathway have been identified, yet targeted therapies show little efficacy in the clinics. No drugs are currently available for the G protein alpha subunitsGNAQ and GNA11, which are the most frequent driver mutations in UM. Drugs targeting the YAP–TAZ pathway that is also activated in UM, the tumor-suppressor gene BRCA1 Associated Protein 1 (BAP1) and the Splicing Factor 3b Subunit 1 gene (SF3B1) whose mutations are associated with metastatic risk, have not been developed yet. Immunotherapy is highly effective in cutaneous melanoma but yields only poor results in the treatment of UM: anti-PD-1 and anti-CTLA-4 blocking antibodies did not meet the expectations except for isolated cases. Here, we discuss how the improved knowledge of the tumor microenvironment and of the cross-talk between tumor and immune cells could help to reshape anti-tumor immune responses to overcome the intrinsic resistance to immune checkpoint blockers of UM. We critically review the dogma of low mutational load, the induction of immune-suppressive cells, and the expression of alternative immune checkpoint molecules. We argue that immunotherapy might still be an option for the treatment of UM.

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“…The metastatic tumor develops with from infiltrative pattern to nodular growth pattern, and the infiltrating immune cells change from natural killer (NK) cells to CD3-positive lymphocytes according to tumor growth (7). Thus not only adoptive but also innate immune cells including NK cells contribute to the formation of tumor microenvironment (8). However, on the other hand, uveal melanoma is refractory to immunotherapy, the standard treatment for metastatic melanoma, with the median survival of patients diagnosed with liver metastases of uveal melanoma being only several months (9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

CD8 Positive T Lymphocyte Infiltration of Liver Metastases of Uveal Melanoma: A Case Report

et al. 2021

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A 78-year-old Japanese man was referred for examination of multiple small nodules on his liver detected by magnetic resonance imaging (MRI). These small nodules were hyperintense on T1-weighted MRI, and were in hepatobiliary phase on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid enhanced MRI. Five years earlier, he had undergone curative enucleation of his left eye for uveal melanoma. US-guided biopsy revealed that the liver nodules were metastases of melanoma. Pathological examination also showed infiltration of CD8 positive T lymphocytes. The metastatic nodules remained unchanged for more than 2 years and he was not further treated. This pathology and clinical course suggest that the systemic immune response of the host could suppress hepatic metastases of uveal melanoma.

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Role of Natural Killer Cells in Uveal Melanoma

Cited by 20 publications

References 171 publications

Features of the lymphocytic microenvironment in metastatic uveal melanoma

Features of the lymphocytic microenvironment in metastatic uveal melanoma

How to Make Immunotherapy an Effective Therapeutic Choice for Uveal Melanoma

CD8 Positive T Lymphocyte Infiltration of Liver Metastases of Uveal Melanoma: A Case Report

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