Deciphering the intricate relationship between macrophages, pigmentation, and prognosis in uveal melanoma.

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, though less common, in relatively low-risk Asian population. Research shows that proangiogenic M2 macrophages and monosomy 3 play a significant role in UM progression. Our aim is to investigate the impact of tumor-associated macrophages in UM and examine their correlation with monosomy 3 & pigmentation. TEM was used to analyze the morphology of macrophages in UM. Forty UM samples underwent FISH for monosomy 3 identification. Immunohistochemistry was done to assess M2/M1 macrophages on 82 UM tissue samples. IL-10 and IL-12 expression was quantified in UM serum samples by ELISA. Expression of all markers was correlated with pigmentation markers (TYRP1, TYRP2, SILV & MITF). Prognostic outcomes were determined using the Cox proportional hazard model & log-rank test. Increased expression of M2/M1 macrophages was observed in 31 UM cases, which correlated with 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 MFS was observed in UM patients with high M2/M1 macrophage expression (p=0.001). High pigmentation and increased M2 macrophage density could impact the tumor microenvironment in UM. This could contribute to ineffective antitumor immune responses in UM patients. Our findings suggest avenues for developing novel therapeutic approaches to counteract these immunosuppressive effects in UM.