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New prospects on the NKG2D/NKG2DL system for oncology
Evelyn Ullrich1, Joachim Koch2, Adelheid Cerwenka3
1Children's Hospital; Department of Pediatric Hematology and Oncology; Goethe-University Frankfurt am Main; Frankfurt am Main, Germany ; Center for Cell and Gene Therapy; Goethe University Frankfurt am Main; Frankfurt am Main, Germany.
Abstract:
The activating immunoreceptor NKG2D endows cytotoxic lymphocytes with the capacity to recognize and eliminate infected or malignant cells. The recognition of such harmful cells is enabled by binding of NKG2D to various MHC class I-related glycoproteins, which are upregulated in the course of viral infection or malignant transformation. The past years have witnessed substantial progress in our understanding of the mechanisms underlying the regulation of NKG2D ligands (NKG2DLs) by malignant cells, of tumor-associated countermeasures promoting escape from NKG2D-dependent immunosurveillance, and of therapeutic measures that may bolster the NKG2D/NKG2DL system against malignancies. Here, we summarize the current knowledge on the NKG2D/NKG2DL system and outline opportunities to exploit the tumoricidal function of NKG2D for anticancer immunotherapy.
Insights
The NKG2D receptor helps cytotoxic lymphocytes identify and destroy harmful cells. Understanding NKG2D ligands (NKG2DLs) offers new anticancer immunotherapy strategies.
Area of Science:
- Immunology
- Cancer Biology
- Immunotherapy
Background:
- The activating immunoreceptor NKG2D is crucial for recognizing and eliminating infected or malignant cells.
- NKG2D functions by binding to MHC class I-related glycoproteins, which are upregulated during viral infection and malignant transformation.
- Malignant cells can evade NKG2D-mediated immune surveillance through regulatory mechanisms and countermeasures.
Approach:
- This review summarizes current knowledge of the NKG2D/NKG2DL system.
- It details mechanisms of NKG2DL regulation by cancer cells.
- It explores tumor-associated strategies for immune escape and therapeutic interventions.
Key Points:
- NKG2D ligands (NKG2DLs) are upregulated on stressed cells, marking them for destruction by cytotoxic lymphocytes.
- Malignant cells employ diverse strategies to downregulate NKG2DLs or inhibit NKG2D function, facilitating immune evasion.
- Therapeutic strategies aim to restore or enhance NKG2D-mediated anti-tumor immunity.
Conclusions:
- The NKG2D/NKG2DL axis is a critical component of anti-tumor immunity.
- Targeting the NKG2D pathway holds significant promise for developing novel cancer immunotherapies.
- Further research into NKG2D regulation and its exploitation is essential for effective cancer treatment.
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