The decrease in NKG2D+ Natural Killer cells in peripheral blood of patients with metastatic colorectal cancer

Abstract

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.

Tuberculosis patients display a high proportion of CD8+ T cells with a high cytotoxic potential

“…Mtb infection was not found to decrease the NKG2D expression of CD8 + T cells. However, in cancer models, the decreased expression of NKG2D both on CD8 + T and on NK cellular surfaces was demonstrated, and it was determined to be a mechanism that compromises cell function and promotes tumor immune escape . Regarding human CD56 + CD8 + T cells, it has been demonstrated that this subpopulation is less vigorous in terms of proliferation, after which it is bound to classical class I HLA.…”

“…However, in cancer models, the decreased expression of NKG2D both on CD8 + T and on NK cellular surfaces was demonstrated, and it was determined to be a mechanism that compromises cell function and promotes tumor immune escape. 26,27 Regarding human CD56 + CD8 + T cells, it has been demonstrated that this subpopulation is less vigorous in terms of proliferation, after which it is bound to classical class I HLA. This subpopulation displays enhanced natural cytotoxicity activity and cytokine secretion, and it was proposed that the frequency of CD56 + CD8 + T cells could be affected by cytomegalovirus infection and aging.…”

Angiogenin and the MMP9‐TIMP2 axis are up‐regulated in proangiogenic, decidual NK‐like cells from patients with colorectal cancer

“…NK cells are innate immune-effector cells involved in tumor surveillance (10,53,54); however, the functionality of NK cells is altered in patients with cancer (8,10,54), showing reduced degranulation capability and cytotoxicity. Despite their low numbers in TUMs, the presence of CRC infiltrating NK cells can influence patient outcome (14,(55)(56)(57). A significant down-regulation of several activatory receptors, including CD16, NKG2D, NKp30, NKp44, NKp46, CD161, and DNAM-1, has been observed in CRC circulating and tissue-infiltrating NK cells (58).…”

FCGR2A, FCGR3Apolymorphisms and therapeutic efficacy of anti-EGFR monoclonal antibody in metastatic colorectal cancer

“…NK cell was generally scarce within CRC tumor tissues, on the contrary, normal level of NK cell was examined in adjacent normal mucosa [ 39 ]. Meanwhile, a significant reduction in the percentage of NKG2D+NK cell was observed in peripheral blood of metastatic colon cancer patients [ 40 ]. Additionally, tumor-associated macrophage (TAM) is one of the most frequently found immune cells in the tumor microenvironment [ 41 ].…”