Infiltrating Lymphocytes and Antigen Expression in Uveal Melanoma

Meecham, William J.; Char, Devron H.; Kaleta-Michaels, Shawnya

doi:10.1159/000267140

Cited by 33 publications

(33 citation statements)

References 18 publications

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“…Tumor infiltrating lymphocytes have been detected in variable proportions in UMM (30,37), with either a predominance ofCD3+/CD8+ cells or CD4+ and CD8+ cells present in equal amounts (27,30) or a predominance of CDI6+ NK cells (29). Ma and co-workers (38) showed that, during the early stage of tumor growth, CD4+ cells were the dominant T cell population.…”

Section: Discussionmentioning

confidence: 99%

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Tumor Infiltrating Lymphocytes in Uveal Melanoma: A Link with Clinical Behavior?

Staibano¹,

Mascolo²,

Tranfa

et al. 2006

Int J Immunopathol Pharmacol

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Experimental and clinical evidence indicate that immunological mechanisms might be important in the clinical course of uveal malignant melanoma (UMM). We analyzed the amount and phenotype of tumor infiltrating lymphocytes (TIL) and the expression of the apoptosis-inducing molecule Fas and its ligand, FasL, on tumor cells and TIL in a selected series of UMM with the aim to establish if a correlation between their expression and the clinical behavior of UMM exists. TIL phenotype and Fas/FasL expression were evaluated by immunohistochemistry in 61 cases of formalin-fixed, paraffin-embedded UMM. Results were compared with the follow-up data of patients. Most of the UMM showed a prevalence of CD8+ CD3+ T lymphocytes, or CD4+ and CD8+ cells in equal amounts. UMM showed a variable expression of FasL, ranging from 0 to > 40% of neoplastic cells. Fas was always expressed in TIL, although with a variable extent. A subgroup of UMM showed in TIL a strongly reduced or even absent expression ofTCR~-chain, involved in activation ofT-lymphocytes. This subgroup was characterized by a worse outcome. We hypothesized that an impaired cytotoxic immune response due to the loss of the~ chain expression plays a primary role in the biological course of UMM. Our results indicate that the overcoming of the impairment of TCR function may represent a prerequisite for the development of new therapeutic strategies for managing UMM, suggesting that elimination of tumor cells may be possible by activation of cytotoxic cells present within ocular melanomas.Uveal malignant melanoma (UMM) is the most common malignant primary intra-ocular tumor in adults (1-4). It accounts for 70-88% of all ocular tumors, with an annual incidence of approximately 6 cases per milIion per year (1-4). The therapy of UMM is problematic due to the high rate of metastatic dissemination (5). Treatment therapies for this tumor warrant further studies. To date, enucleation remains as effective as the recent eyesparing approaches (6-7). When metastatic disease is diagnosed, patient survival is generally less than 7 months (8-11). During the "dormant" period from diagnosis of primitive tumor and the occurrence of metastasis, chemo-and immunotherapy have also been considered (12).UMM arises in the immune-privileged ocular

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Section: Discussionmentioning

confidence: 99%

“…The effective role of tumor-infiltrating lymphocytes (TIL) in biological behavior of UMM is still far from being clarified (3,13, IS, [27][28][29]. There is, to date, no convincing evidence that a better prognosis is associated with lymphocytic infiltration in UMM (15,(30)(31).…”

mentioning

confidence: 99%

Tumor Infiltrating Lymphocytes in Uveal Melanoma: A Link with Clinical Behavior?

Staibano¹,

Mascolo²,

Tranfa

et al. 2006

Int J Immunopathol Pharmacol

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“…A large immunohistochemical study showed that 134 out of 1,078 tumors contained a lymphocytic infiltrate (100 or more lymphocytes per 20 high-power (×400) microscopic fields) [9]. A second study of 27 tumors showed that lymphocyte infiltration is variable when tumor suspensions were analyzed by flow cytometry and a substantial proportion of TIL were CD8+ T cells, with some CD4+ T cells [10]. These subpopulations were respectively named T suppressor/cytotoxic T lymphocytes (CTL) and helper T cells, but they were not functionally assessed.…”

Section: Tumor Microenvironmentmentioning

confidence: 99%

Uveal Melanoma: The Inflammatory Microenvironment

Bronkhorst

Jager²

2012

J Innate Immun

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Uveal melanoma is a highly malignant intraocular tumor with quite homogeneous tumor tissue and a diffuse leukocytic infiltration. In contrast with many other malignancies, the presence of infiltrating macrophages and T cells is associated with a poor prognosis rather than a good one. The clear link between inflammation and cancer in this malignancy provides a paradigm for macrophage plasticity and function. Macrophages in uveal melanoma have an M2-like phenotype and are associated with the loss of one specific chromosome – monosomy 3. The central players involved in this process and discussed in this review include macrophages, T lymphocytes, chemokines and cytokines, including the macrophage-attraction molecules. When a tumor acquires the ability to release significant amounts of macrophage-attraction molecules it causes the expansion of a population of myeloid immature cells that may not only help the tumor to suppress immune reactions but also aid in the construction of new blood vessels for tumor growth. A better understanding of the molecular basis of a local myelomonocytic cell population will bring a better understanding of the immunopathology of this disease and will lead to therapeutic interventions in uveal melanoma. This review focuses on the roles of the local inflammatory microenvironment in the development and progression of uveal melanoma.

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“…In one study TIL were predominantly CD8+ T cells,22 in another study CD4 + and CD8+ cells were present in equal amounts, 23 and in yet another report CD16+ natural killer (NK) cells were the dominant lympho cyte population, accounting for 41 % of the TIL. 24 The prognostic significance of TIL in uveal melano mas is also unclear.…”

Section: Role Of Intraocular Tumour Infiltrating Lymphocytesmentioning

confidence: 95%