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- Title
Regulation of NKG2D Stress Ligands and Its Relevance in Cancer Progression.
- Authors
Jones, Amber B.; Rocco, Abbey; Lamb, Lawrence S.; Friedman, Gregory K.; Hjelmeland, Anita B.
- Abstract
Simple Summary: Immune surveillance during periods of cellular stress is necessary to maintain homeostasis. In distressed cells, the expression of stress (natural killer group 2 member D (NKG2D)) ligands is induced on cells to promote recognition by cytotoxic immune populations. This process is exemplified during cancer initiation, progression, and maintenance. Unfortunately, cancer cell adaptation yields multiple mechanisms to evade immune cell recognition. Therefore, extensive efforts have been investigated to induce stress ligands on tumor cells to complement immunotherapy efforts. In this review, we provide updates on the current regulatory mechanisms involved with both stress ligand induction and repression and offer areas of consideration as research on this topic progresses. Under cellular distress, multiple facets of normal homeostatic signaling are altered or disrupted. In the context of the immune landscape, external and internal stressors normally promote the expression of natural killer group 2 member D (NKG2D) ligands that allow for the targeted recognition and killing of cells by NKG2D receptor-bearing effector populations. The presence or absence of NKG2D ligands can heavily influence disease progression and impact the accessibility of immunotherapy options. In cancer, tumor cells are known to have distinct regulatory mechanisms for NKG2D ligands that are directly associated with tumor progression and maintenance. Therefore, understanding the regulation of NKG2D ligands in cancer will allow for targeted therapeutic endeavors aimed at exploiting the stress response pathway. In this review, we summarize the current understanding of regulatory mechanisms controlling the induction and repression of NKG2D ligands in cancer. Additionally, we highlight current therapeutic endeavors targeting NKG2D ligand expression and offer our perspective on considerations to further enhance the field of NKG2D ligand biology.
- Subjects
THERAPEUTIC use of antineoplastic agents; DISEASE progression; PHYSIOLOGICAL stress; CELL receptors; TUMORS; IMMUNOTHERAPY
- Publication
Cancers, 2022, Vol 14, Issue 9, pN.PAG
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers14092339