Melanoma - a tumor formed by melanocyte lesions, normal melanocytes mostly exist in the basal layer of the skin epidermis, it produces melanin and is transmitted to the surrounding keratinocytes, melanin stays on the nuclei of these cells to prevent chromosomes from being damaged by light radiation; When long-term exposure to sunlight ultraviolet rays, fair skin, poor protection against ultraviolet rays, normal melanocytes in the body will undergo genetic mutations, into malignant cells that can reproduce indefinitely, expand, and then lead to melanoma, this cutaneous melanoma (CM) is common in whites, yellow and black people The probability of suffering is relatively small, but melanoma is not the only one, studies have shown that in Asian populations, multiple acral melanoma (AM), such as fingers, toes, foot bottom position, etc. It accounts for about 50% of East Asian melanoma cases. The extremity is rarely exposed to ultraviolet rays, so the cause of AM is different from that of CM, and the different pathogenesis eventually leads to some immunotherapy methods suitable for CM, which are not ideal in AM patients.
Schematic diagram of melanoma
In order to better understand acral melanoma, on November 25, 2022, Tianjin Medical University Yang Jilong, Li Xiangchun and Chen Kexin jointly published a research paper entitled "A single-cell analysis reveals tumor heterogeneity and immune environment of acral melanoma" in Nature Communications. Single-cell RNA sequencing was performed on 63,394 cells from 5 AM and 3 CM samples to study tumor heterogeneity and immune environment. The study found that AM had a pronounced immunosuppressive state compared to CM, and PD-1 and TIM-3 were highly expressed in depleted CD8+ T cells of AM.
Figure 1 scRNA-seq analysis of AM and CM tumor microenvironments
In addition to single-cell sequencing, the research team also used the Absin five-color multiplex fluorescence immunohistochemical staining kit (ABS50013) to multiplex relevant immune targets in situ for further demonstration from the protein level. The results showed that CD8+ T cells in the depleted state of acral melanoma (AM) were highly expressed TIM-3 and PD-1 (Figure 2). After anti-PD-1 immunotherapy alone, the proportion of CD8+ T cells in AM patients decreased compared with pre-treatment cells, while the proportion of CD4+ T cells and B cells increased, indicating that anti-PD-1 therapy alone did not respond to AM patients (Figure 3).
Figure 2
Figure 3
In addition to exploring the immune microenvironment of AM, the research team also found that the combination of anti-PD-1 and anti-TIM-3 drugs significantly increased the apoptosis ratio of AM tumor cells. Immunotherapy combined with EGFR pathway-related genes may also improve the effectiveness of immunotherapy in AM patients. It provides valuable information for the development of more effective therapeutic targets and immunotherapy-related biomarkers for acral patients.
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Zhang C, Shen H, Yang T, Li T, Liu X, Wang J, Liao Z, Wei J, Lu J, Liu H, Xiang L, Yang Y, Yang M, Wang D, Li Y, Xing R, Teng S, Zhao J, Yang Y, Zhao G, Chen K, Li X, Yang J. A single-cell analysis reveals tumor heterogeneity and immune environment of acral melanoma. Nat Commun. 2022 Nov 25;13(1):7250. doi: 10.1038/s41467-022-34877-3. PMID: 36433984; PMCID: PMC9700682.