Abstract
CD3+CD56+ natural killer T (NKT)-like cells are a group of CD3+ T cells sharing characteristics of NK and T cells and constitute a major component of host anti-tumor immune response in human cancer. However, the nature, function and clinical relevance of CD3+CD56+ NKT-like cells in human gastric cancer (GC) remain unclear. In this study, we showed that the frequencies of CD3+CD56+NKT-like cells in GC tumors were significantly decreased and low levels of tumor-infiltrating CD3+CD56+ NKT-like cells were positively correlated with poor survival and disease progression. Most CD3+CD56+NKT-like cells in GC tumors were CD45RA−CD27+/− central/effector-memory cells with decreased activity and lower expression levels of CD69, NKG2D and DNAM-1 than those in non-tumor tissues. We further observed that tumor-infiltrating CD3+CD56+ NKT-like cells had impaired effector function as shown by decreased IFN-γ, TNF-α, granzyme B and Ki-67 expression. Moreover, in vitro studies showed that soluble factors released from GC tumors could induce the functional impairment of CD3+CD56+ NKT-like cells. Collectively, our data indicate that decreased tumor-infiltrating CD3+CD56+ NKT-like cells with impaired effector function are associated with tumor progression and poor survival of GC patients, which may contribute to immune escape of GC.
Highlights
Gastric cancer (GC) is the fourth most common cancer worldwide often with poor prognosis [1]
We show that decreased levels of tumor-infiltrating CD3+CD56+ natural killer T (NKT)-like cells with functional impairment correlated with tumor progression and poor overall survival of gastric cancer (GC) patients
We found that there was no difference in the frequencies of circulating CD3+CD56+ NKT-like cells between healthy individuals and GC patients (Figure 1B, 5.17%, 0.37%-23.01% vs. 5.55%, 1.22%-12.04%, P>0.05)
Summary
Gastric cancer (GC) is the fourth most common cancer worldwide often with poor prognosis [1]. Once TCR ligation, CD3+CD56+ NKT-like cells can be activated to secrete cytotoxic enzymes and cytokines to kill target cells [7]. Studies focusing on the functional activity of CD3+CD56+NKT-like cells showed that the cytotoxicity and cytokine production of these cells are impaired in haematological malignancies and other solid tumors, such as chronic lymphocytic leukemia and ovarian cancer [11, 12]. In acute leukemia, higher numbers of CD3+CD56+NKT-like cells were observed in the peripheral blood, their functions were significantly impaired [13]. Taken together, these data suggest that the anti-tumor activity of CD3+CD56+ NKT-like cells is likely altered in the tumor microenvironment. The nature, function and clinical relevance of CD3+CD56+ NKT-like cells in GC patients remain largely unexplored
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