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Published on: May 17, 2024
NKG2D-deficient mice are defective in tumor surveillance in models of spontaneous malignancy
Nadia Guerra1, Ying Xim Tan, Nathalie T Joncker
1Department of Molecular and Cell Biology, 489 Life Sciences Addition, University of California, Berkeley, Berkeley, CA 94720, USA.
Abstract:
Ligands for the NKG2D stimulatory receptor are frequently upregulated on tumor lines, rendering them sensitive to natural killer (NK) cells, but the role of NKG2D in tumor surveillance has not been addressed in spontaneous cancer models. Here, we provided the first characterization of NKG2D-deficient mice, including evidence that NKG2D was not necessary for NK cell development but was critical for immunosurveillance of epithelial and lymphoid malignancies in two transgenic models of de novo tumorigenesis. In both models, we detected NKG2D ligands on the tumor cell surface ex vivo, providing needed evidence for ligand expression by primary tumors. In a prostate cancer model, aggressive tumors arising in NKG2D-deficient mice expressed higher amounts of NKG2D ligands than did similar tumors in wild-type mice, suggesting an NKG2D-dependent immunoediting of tumors in this model. These findings provide important genetic evidence for surveillance of primary tumors by an NK receptor.
Insights
Natural killer (NK) cell receptor NKG2D is crucial for immunosurveillance against epithelial and lymphoid cancers. NKG2D deficiency accelerates tumor growth, highlighting its role in preventing cancer development.
Area of Science:
- Immunology
- Cancer Biology
- Genetics
Background:
- Ligands for the NKG2D receptor are often found on tumor cells, making them vulnerable to natural killer (NK) cells.
- The function of NKG2D in tumor surveillance within spontaneous cancer models remains largely uninvestigated.
Purpose of the Study:
- To characterize NKG2D-deficient mice and assess the role of NKG2D in spontaneous tumor development and immunosurveillance.
- To investigate NKG2D ligand expression on primary tumors in vivo.
Main Methods:
- Generation and characterization of NKG2D-deficient mice.
- Utilized two transgenic models of de novo tumorigenesis (epithelial and lymphoid malignancies).
- Analyzed NK cell development, tumor progression, and NKG2D ligand expression on tumor cells ex vivo.
Main Results:
- NKG2D is not essential for NK cell development but is critical for immunosurveillance against epithelial and lymphoid cancers.
- NKG2D ligands were detected on primary tumor cells in both transgenic models.
- In a prostate cancer model, tumors in NKG2D-deficient mice showed increased aggressiveness and higher NKG2D ligand expression, suggesting immunoediting.
Conclusions:
- NKG2D plays a vital role in the immunosurveillance of spontaneous tumors, particularly epithelial and lymphoid malignancies.
- The study provides genetic evidence for NK receptor-mediated surveillance of primary tumors.
- NKG2D-dependent immunoediting influences tumor progression and ligand expression.
