Deciphering the Intricate Relationship Between Macrophages, Pigmentation, and Prognosis in Uveal Melanoma

IF 5.1 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Laboratory Investigation Pub Date : 2024-11-02 DOI:10.1016/j.labinv.2024.102167

Jayanti Jha , Mithalesh Kumar Singh , Lata Singh , Neelam Pushker , Aanchal Kakkar , Rachna Meel , Neiwete Lomi , Sameer Bakhshi , Tapas Chandra Nag , Chanda Panwar , Seema Sen , Seema Kashyap

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引用次数: 0

Abstract

High pigmentation and the abundance of M2 macrophages have been identified as negative predictors in uveal melanoma (UM). Risk factors associated with UM that are prevalent in high-risk White populations are still present, although less common, in relatively low-risk Asian populations. Research indicates that proangiogenic M2 macrophages and monosomy 3 play significant roles in UM progression. Our aim was to investigate the impact of tumor-associated macrophages in UM and examine their correlation with monosomy 3 and pigmentation. Transmission electron microscopy was used to analyze the morphology of macrophages in UM. Forty UM samples underwent fluorescent in situ hybridization for monosomy 3 identification. Immunohistochemistry was done to assess M2/M1 macrophages on 82 UM tissue samples. IL-10 and IL-12 expressions were quantified in UM serum samples by enzyme-linked immunosorbent assay. The expression of all markers was correlated with pigmentation markers (tyrosinase-related protein 1, tyrosinase-related protein 2, silver protein, and microphthalmia-associated transcription factor). Prognostic outcomes were determined using the Cox proportional hazard model and log-rank tests. Increased expression of M2/M1 macrophages was observed in 31 UM cases, which correlated with the high expression of pigmentation markers. IL-10 concentration was high in UM cases. Monosomy 3 was evident in 50% of UM cases and significantly associated with increased immunoexpression of M2/M1 macrophages and pigmentation markers. Reduced metastasis-free survival was observed in patients with UM with high M2/M1 macrophage expression (P = .001). High pigmentation and increased M2 macrophage density could impact the tumor microenvironment in UM. This could contribute to ineffective antitumor immune responses in patients with UM. Our findings suggest avenues for developing novel therapeutic approaches to counteract these immunosuppressive effects in UM.

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破解葡萄膜黑色素瘤中巨噬细胞、色素沉着和预后之间的复杂关系。

高色素沉着和大量的 M2 巨噬细胞已被确定为葡萄膜黑色素瘤（UM）的负面预测因素。在高风险的白人人群中普遍存在的与葡萄膜黑色素瘤相关的风险因素，在风险相对较低的亚裔人群中仍然存在，但并不常见。研究表明，促血管生成的 M2 巨噬细胞和单体 3 在黑色素瘤的发展过程中起着重要作用。我们的目的是研究肿瘤相关巨噬细胞对脐带癌的影响，并探讨其与单体3型和色素沉着的相关性。TEM 被用来分析 UM 中巨噬细胞的形态。对 40 份 UM 样本进行 FISH 检测，以确定单体 3 型。对 82 个 UM 组织样本的 M2/M1 巨噬细胞进行了免疫组化评估。用酶联免疫吸附法对 UM 血清样本中 IL-10 和 IL-12 的表达进行了量化。所有标记物的表达均与色素标记物（TYRP1、TYRP2、SILV和MITF）相关。采用 Cox 比例危险模型和对数秩检验确定预后结果。在 31 例 UM 病例中观察到 M2/M1 巨噬细胞表达增加，这与色素沉着标记物的高表达相关。UM病例中IL-10浓度较高。50%的 UM 病例中存在明显的单体 3，并且与 M2/M1 巨噬细胞和色素标记物的免疫表达增加有显著关联。在 M2/M1 巨噬细胞高表达的 UM 患者中观察到 MFS 降低（p=0.001）。高色素沉着和 M2 巨噬细胞密度增加可能会影响 UM 的肿瘤微环境。这可能会导致 UM 患者的抗肿瘤免疫反应无效。我们的发现为开发新型治疗方法提供了途径，以抵消 UM 的这些免疫抑制效应。

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来源期刊

Laboratory Investigation 医学-病理学

CiteScore

8.30

自引率

0.00%

发文量

125

审稿时长

2 months

期刊介绍： Laboratory Investigation is an international journal owned by the United States and Canadian Academy of Pathology. Laboratory Investigation offers prompt publication of high-quality original research in all biomedical disciplines relating to the understanding of human disease and the application of new methods to the diagnosis of disease. Both human and experimental studies are welcome.