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Abstract:Background: Natural killer (NK) cells play important roles in the immune defense against tumors such as colorectal cancer. In humans, NKG2D is an activating immune receptor constitutively expressed in most cytotoxic lymphocytes including NK and CD8+ T cells. In this study, the expression of NKG2D molecule was investigated in peripheral blood NK cells from colorectal cancer patients and compared with healthy subjects. Methods: We studied 21 non-metastatic (low-grade), 17 non-metastatic (high-grade), 16 metastatic colorectal cancer patients, and 24 healthy controls. Peripheral blood samples were obtained to isolate peripheral blood mononuclear cells (PBMCs) and the percentage of peripheral blood NKG2D+CD3-CD56+ NK cells was analyzed by fl ow cytometry. The expression of NKG2D at mRNA level was also measured by real-time PCR in both, patients and control subjects. Results: The results showed a signifi cant reduction in the percentage of NKG2D+NK cells as well as NKG2D mRNA expression in peripheral blood of metastatic colon cancer patients. Conclusion: This result suggests that decreased expression of activating NKG2D receptor in metastatic colorectal cancer might compromise NK cell function and allow tumor to evade immunity (Tab. 3, Fig. 4, Ref. 33 Acknowledgements: Our thanks go to the vice chancellor for research, Isfahan University of Medical Sciences for supporting this research (project registration number: 189022). Also, we would like to thank all patients and healthy volunteers who participated in this study.

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OBJECTIVE: Colorectal cancer (CRC) is one of the main causes of cancer deaths in the world. This cancer can be divided into non-metastatic and metastatic CRC stages. CD3+CD56+ NKT cell subsets are a minor T cell subset in peripheral blood and conduct the killing of tumor cells in direct manner. Little is obvious about levels and surface markers of these cells such as NKG2D in different cancers, especially in CRC. METHODS: We included 15 non-metastatic (low-grade), 11 non-metastatic (high-grade), 10 metastatic colorectal cancer patients and 18 healthy controls. The percentages of CD3+CD56+ NKT cells and NKG2D+CD56+ NKT cells from samples were analyzed by fl ow cytometry in peripheral blood mononuclear cells (PBMCs) of samples. RESULTS: We found that there was a signifi cantly lower number of NKG2D+CD3+CD56+ cells in peripheral blood of patients with metastatic colorectal cancer compared with normal controls (77.53 ± 5.79 % vs 90.74 ± 9.84 %; p<0.01). CONCLUSION: The fact that frequency of NKG2D+CD56+ NKT cells was signifi cantly lower in patients with metastatic colorectal cancer compared to healthy controls strengthens the hypothesis that NKT cells can play a substantial role in the protection against human colorectal cancer, and this opens up avenues for novel studies about elucidating the other aspects of tumor surveillance in CRC progression and immunotherapy (Tab. 2, Fig. 2, Ref. 46). Text in PDF www.elis.sk.