MAP-激酶（MAPK）通路中的三个主要通路，ERK1/2、p38和JNK/SAPK，是核“激素”受体超家族（NHRSF）的上游调控因子，其中乳腺癌中的雌激素受体是一个典型例子。这些配体激活的转录因子发挥非基因组和基因组功能，它们要么经过翻译后磷酸化后修饰，要么直接与MAPK通路的组分相互作用，从而调节其对细胞分化、增殖、代谢和宿主免疫中所涉及的靶基因的转录活性。这种分子交互作用不仅发生在正常上皮或肿瘤细胞中，还发生在肿瘤基质组织微环境中的一大批自适应免疫系统和固有免疫系统的免疫细胞中。因此，MAPK和NHRSF通路的药物治疗潜力提示了干预治疗的可能性，特别是对于肿瘤免疫治疗。本综述总结了人类肿瘤（包括实体肿瘤和白血病）中NHRSF亚类的表达和功能的现有文献，以及它们与当前临床批准的对免疫检查点分子（如PD1）的治疗联合应用的效果。

The three major MAP-kinase (MAPK) pathways, ERK1/2, p38 and JNK/SAPK, are upstream regulators of the nuclear "hormone" receptor superfamily (NHRSF), with a prime example given by the estrogen receptor in breast cancer. These ligand-activated transcription factors exert non-genomic and genomic functions, where they are either post-translationally modified by phosphorylation or directly interact with components of the MAPK pathways, events that govern their transcriptional activity towards target genes involved in cell differentiation, proliferation, metabolism and host immunity. This molecular crosstalk takes place not only in normal epithelial or tumor cells, but also in a plethora of immune cells from the adaptive and innate immune system in the tumor-stroma tissue microenvironment. Thus, the drugability of both the MAPK and the NHRSF pathways suggests potential for intervention therapies, especially for cancer immunotherapy. This review summarizes the existing literature covering the expression and function of NHRSF subclasses in human tumors, both solid and leukemias, and their effects in combination with current clinically approved therapeutics against immune checkpoint molecules (e.g., PD1).