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

Elke Burgermeister1

  • 1Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany.

International Journal of Molecular Sciences
|October 14, 2023
PubMed

Insights

Mitogen-activated protein kinase pathways regulate nuclear receptors (NRSF), which sense environmental cues. NRSF subclasses in cancers and immune cells offer potential for novel combination therapies with immune checkpoint inhibitors.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Immunology

Background:

  • Mitogen-activated protein kinase (MAPK) pathways (ERK1/2, p38, JNK/SAPK) are key regulators of the nuclear receptor superfamily (NRSF).
  • NRSF are ligand-activated transcription factors sensing diverse signals like hormones, metabolites, xenobiotics, and immune mediators.
  • NRSF act as crucial sensors translating environmental information to the genome, with many former "orphan" receptors now having identified ligands.

Purpose of the Study:

  • To review the expression and function of NRSF subclasses in human solid tumors and hematopoietic malignancies.
  • To explore the modulatory effects of NRSF on innate and adaptive immune cells.
  • To highlight opportunities for combination therapies involving NRSF and existing cancer treatments.

Main Methods:

  • Literature review of existing studies on NRSF in cancer and immunity.
  • Analysis of NRSF expression and function in various cancer types.
  • Examination of NRSF interactions with immune cells, including macrophages, dendritic cells, and T cell subsets.

Main Results:

  • NRSF subclasses are expressed in both solid tumors and hematopoietic malignancies.
  • NRSF influence the function of innate immune cells (macrophages, dendritic cells) and adaptive immune cells (T cell subsets).
  • Preclinical data suggest potential for NRSF-targeting therapies, particularly in combination with immune checkpoint inhibitors like PD1.

Conclusions:

  • NRSF play a significant role in cancer biology and immune modulation.
  • Identification of ligands for NRSF opens avenues for therapeutic interventions.
  • Further clinical validation is needed for combination therapies targeting NRSF and immune checkpoints in cancer treatment.
Keywords:
MAPKcancerimmunotherapykinasemetabolismnuclear receptorxenobiotics

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