PDF(Pubmed)
Abstract：
CD36 expression in both immune and non-immune cells is known to be directly involved in cancer metastasis. Extracellular vesicles (EVs) secreted by malignant melanocytes play a vital role in developing tumor-promoting microenvironments, but it is unclear whether this is mediated through CD36. To understand the role of CD36 in melanoma, we first analyzed the SKCM dataset for clinical prognosis, evaluated the percentage of CD36 in lymphatic fluid-derived EVs (LEVs), and tested whether melanoma-derived EVs increase CD36 expression and induce M2-macrophage-like characteristics. Furthermore, we performed a multiplex immunofluorescence (MxIF) imaging analysis to evaluate the CD36 expression and its colocalization with various other cells in the lymph node (LN) of patients and control subjects. Our findings show that cutaneous melanoma patients have a worse clinical prognosis with high CD36 levels, and a higher percentage of CD36 in total LEVs were found at baseline in melanoma patients compared to control. We also found that monocytic and endothelial cells treated with melanoma EVs expressed more CD36 than untreated cells. Furthermore, melanoma-derived EVs can regulate immunosuppressive macrophage-like characteristics by upregulating CD36. The spatial imaging data show that cells in tumor-involved sentinel LNs exhibit a higher probability of CD36 expression than cells from control LNs, but this was not statistically significant. Conclusively, our findings demonstrated that CD36 plays a vital role in controlling the immunosuppressive microenvironment in the LN, which can promote the formation of a protumorigenic niche.
摘要：
已知CD36在免疫和非免疫细胞中的表达直接参与癌症转移。恶性黑素细胞分泌的细胞外囊泡（EV）在促进肿瘤微环境的发展中起着至关重要的作用。但尚不清楚这是否通过CD36介导.了解CD36在黑色素瘤中的作用，我们首先分析了SKCM数据集的临床预后，评估了淋巴液衍生的电动汽车（LEV）中CD36的百分比，并测试黑色素瘤衍生的EV是否增加CD36表达并诱导M2-巨噬细胞样特征。此外，我们进行了多重免疫荧光(MxIF)成像分析,以评估患者和对照组淋巴结(LN)中CD36的表达及其与各种其他细胞的共定位.我们的研究结果表明，皮肤黑色素瘤患者的临床预后较差，CD36水平高，与对照组相比,在黑色素瘤患者中,基线时CD36在总LEV中的百分比更高.我们还发现，用黑素瘤EV处理的单核细胞和内皮细胞比未处理的细胞表达更多的CD36。此外，黑色素瘤衍生的EV可以通过上调CD36来调节免疫抑制性巨噬细胞样特征。空间成像数据显示，肿瘤前哨LN中的细胞比对照LN中的细胞表现出更高的CD36表达概率，但这没有统计学意义。最后，我们的发现表明，CD36在控制LN中的免疫抑制微环境中起着至关重要的作用，这可以促进原生生态位的形成。
