Mitogen-Activated Protein Kinase and Exploratory Nuclear Receptor Crosstalk in Cancer Immunotherapy

The three major mitogen-activated protein kinase (MAPK) pathways (ERK1/2, p38, and JNK/SAPK) are upstream regulators of the nuclear receptor superfamily (NRSF). These ligand-activated transcription factors divided into subclasses comprising receptors for endocrine hormones, metabolic compounds (e.g., vitamins, diet), xenobiotics, mediators released from host immune reactions such as tissue injury inflammation. internal external cues place NRSF at frontline sensors translators information environment towards genome. For most former “orphan” receptors, physiological synthetic ligands have been identified, opening intriguing opportunities combination therapies with existing cancer medications. Hitherto, only preclinical data available, warranting further validation in clinical trials patients. current review summarized literature covering expression function human solid tumors hematopoietic malignancies their modulatory effects on innate macrophages, dendritic cells) adaptive (i.e., T cell subsets) cells, encouraging mechanistic pharmacological studies clinically approved therapeutics against checkpoint molecules PD1).