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Despite the remarkable success of immunotherapy in the treatment of melanoma, resistance to these agents still affects patient prognosis and response to therapies. Beta-2-microglobulin (β2M), an important subunit of major histocompatibility complex (MHC) class I, has important biological functions and roles in tumor immunity. In recent years, increasing studies have shown that B2M gene deficiency can inhibit MHC class I antigen presentation and lead to cancer immune evasion by affecting β2M expression. Based on this, B2M gene defect and T cell-based immunotherapy can interact to affect the efficacy of melanoma treatment. Taking into account the many recent advances in B2M-related melanoma immunity, here we discuss the immune function of the B2M gene in tumors, its common genetic alteration in melanoma, and its impact on and related improvements in melanoma immunotherapy. Our comprehensive review of β2M biology and its role in tumor immunotherapy contributes to understanding the potential of B2M gene as a promising melanoma therapeutic target.

Uveal melanoma (UM) is the most frequent primary intraocular malignancy in adults, characterized by melanin depositions in melanocytes located in the uveal tract in the eyes. Differentiation of melanin species (eumelanin and pheomelanin) is crucial in the diagnosis and management of UM, yet it remains inaccessible for conventional histology. Here, we report that femtosecond time-resolved pump-probe microscopy could provide label-free and chemical-specific detection of melanin species in human UM based on their distinct transient relaxation dynamics at the subpicosecond timescale. The method is capable of delineating the interface between melanoma and paracancerous regions on various tissue conditions, including frozen sections, paraffin sections, and fresh tissues. Moreover, transcriptome sequencing was conducted to confirm the active eumelanin synthesis in UM. Our results may hold potential for sensitive detection of tumor boundaries and biomedical research on melanin metabolism in UM.

Abstract Background The MYCN amplification is a defining hallmark of high-risk neuroblastoma. Due to irregular oncogenes orchestration, tumor cells exhibit distinct fatty acid metabolic features from non-tumor cells. However, the function of MYCN in neuroblastoma fatty acid metabolism reprogramming remains unknown. Methods Gas Chromatography-Mass Spectrometer (GC-MS) was used to find the potential target fatty acid metabolites of MYCN. Real-time PCR (RT-PCR) and clinical bioinformatics analysis was used to find the related target genes. The function of the identified target gene ELOVL2 on cell growth was detected through CCK-8 assay, Soft agar colony formation assay, flow Cytometry assay and mouse xenograft. Chromatin immunoprecipitation (ChIP) and Immunoprecipitation-Mass Spectrometer (IP-MS) further identified the target gene and the co-repressor of MYCN. Results The fatty acid profile of MYCN-depleted neuroblastoma cells identified docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid with anti-tumor activity, significantly increased after MYCN depletion. Compared with MYCN single-copy neuroblastoma cells, DHA level was significantly lower in MYCN-amplified neuroblastoma cells. RT-PCR and clinical bioinformatics analysis discovered that MYCN interfered DHA accumulation via ELOVL fatty acid elongase 2 (ELOVL2) which is a rate-limiting enzyme of cellular DHA synthesis. Enforced ELOVL2 expression in MYCN-amplified neuroblastoma cells led to decreased cell growth and counteracted the growth-promoting effect of MYCN overexpression both in vitro and vivo. ELOVL2 Knockdown showed the opposite effect in MYCN single-copy neuroblastoma cells. In primary neuroblastoma, high ELOVL2 transcription correlated with favorable clinical tumor biology and patient survival. The mechanism of MYCN-mediated ELOVL2 inhibition contributed to epigenetic regulation. MYCN recruited PRC1 (Polycomb repressive complex 1), catalysed H2AK119ub (histone 2A lysine 119 monoubiquitination) and inhibited subsequent ELOVL2 transcription. Conclusions The tumor suppressive properties of DHA and ELOVL2 are repressed by the MYCN and PRC1 jointly, which suggests a new epigenetic mechanism of MYCN-mediated fatty acid regulation and indicates PRC1 inhibition as a potential novel strategy to activate ELOVL2 suppressive functions.