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Published on: January 22, 2018
Potential therapeutic strategy for gastric cancer peritoneal metastasis by NKG2D ligands-specific T cells
Xianqiang Liu1, Meili Sun2, Shui Yu3
1Department of Breast and Thyroid Surgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong, People's Republic of China.
Purpose:
Despite advancements in its treatment, gastric cancer continues to be one of the leading causes of cancer deaths worldwide. Adoptive transfer of chimeric antigen receptor-modified T cells is a promising antitumor therapy for many cancers. The purpose of this study was to construct a chimeric receptor linking the extracellular domain of NKG2D to the CD28 and CD3zeta chain intracellular domains to target gastric cancers that expressed NKG2D ligands.
Methods:
Expression of NKG2D ligands including MICA, MICB, and ULBP1-3 in a gastric cancer cell line and primary gastric cancer cells from ascites samples were analyzed using flow cytometry. Co-culture experiments were performed by incubating chNKG2D T cells with gastric cancer cell lines and with primary human gastric cancer cells isolated from ascites and by measuring cytokine and chemokine release and cytotoxicity.
Results:
Gastric cancer cell lines and ascites-derived primary human gastric cancer cells expressed high levels of MICA, MICB, and ULBP2. ChNKG2D T cells secreted proinflammatory cytokines and chemokines when cultured with these cancer cells. In addition, chNKG2D T cells lysed gastric cancer cell lines and the ascites-derived primary human gastric cancer cells.
Conclusion:
These data indicate that treatment with chNKG2D-expressing T cells is a potential immunotherapy for gastric cancer with peritoneal metastasis.
Insights
Engineered T cells targeting NKG2D ligands show promise for treating gastric cancer. This immunotherapy approach demonstrated effectiveness against gastric cancer cells, including those from peritoneal metastasis.
Area of Science:
- Immunology
- Oncology
- Cell Therapy
Background:
- Gastric cancer remains a significant global health challenge with high mortality rates.
- Adoptive cell therapy using chimeric antigen receptor (CAR)-modified T cells offers a promising avenue for cancer treatment.
Purpose of the Study:
- To engineer T cells with a chimeric receptor targeting NKG2D ligands for gastric cancer therapy.
- To investigate the potential of chimeric NKG2D (chNKG2D)-expressing T cells against gastric malignancies.
Main Methods:
- Assessed NKG2D ligand expression (MICA, MICB, ULBP1-3) on gastric cancer cell lines and primary ascites cells via flow cytometry.
- Conducted co-culture experiments with chNKG2D T cells and gastric cancer cells.
- Measured cytokine/chemokine release and cytotoxic activity.
Main Results:
- Gastric cancer cells, including primary ascites-derived cells, exhibited high expression of MICA, MICB, and ULBP2.
- chNKG2D T cells produced pro-inflammatory cytokines and chemokines upon co-culture.
- chNKG2D T cells effectively lysed both gastric cancer cell lines and primary cancer cells.
Conclusions:
- chNKG2D-expressing T cells represent a potential immunotherapy for gastric cancer, particularly for cases with peritoneal metastasis.
- This approach warrants further investigation for clinical application in gastric cancer treatment.
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