男性和女性之间黑色素瘤的生存率存在显着差异，但不能用行为差异来解释。我们和其他人提供的证据表明，这种差异可能是由于 X 失活失败导致第二条 X 染色体免疫相关基因表达增加所致。在本综述中，我们检查了相反观点的证据，即生存差异是由于男性免疫反应较弱造成的。造成这种情况的原因之一可能是 Y 染色体 (LOY) 丢失，尤其是老年男性。所涉及的基因可能在免疫反应中具有直接作用，或者是调节参与免疫反应或肿瘤生长的性别和常染色体基因的非编码RNA。 KDM6C 和 KDM5D 去甲基酶的缺失似乎涉及常见基因。第二个因素似乎是黑色素瘤细胞上雄激素受体（AR）的激活，这增加了黑色素瘤细胞的侵袭性和生长。 AR 诱导 T 细胞耗竭，从而限制针对黑色素瘤的免疫反应，这似乎是一个常见的发现。克服 Y 基因丢失相关影响的治疗方法的开发提出了挑战，但与 AR 信号传导相关的几种途径似乎值得在转移性疾病的治疗中进一步研究。© 2024 作者。色素细胞

Marked differences in survival from melanoma are noted between men and women that cannot be accounted for by behavioral differences. We and others have provided evidence that this difference may be due to increased expression of immune-related genes from the second X chromosome because of failure of X inactivation. In the present review, we have examined evidence for the contrary view that survival differences are due to weaker immune responses in males. One reason for this may be the loss of Y chromosomes (LOY), particularly in older males. The genes involved may have direct roles in immune responses or be noncoding RNAs that regulate both sex and autosomal genes involved in immune responses or tumor growth. Loss of the KDM6C and KDM5D demethylases appeared to common genes involved. The second factor appears to be the activation of androgen receptors (AR) on melanoma cells that increase their invasiveness and growth. Induction of T-cell exhaustion by AR that limits immune responses against melanoma appeared a common finding. The development of treatments to overcome effects related to gene loss on Y poses challenges, but several avenues related to AR signaling appear worthy of further study in the treatment of metastatic disease.© 2024 The Author(s). Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.