Targeting immune inhibitory receptors to restore the function of tumor surrounding T cells could be helpful for immunotherapy of CLL.

Background: In this study, the expression pattern of NKp30 and T cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3), as candidates for activating and inhibitory receptors of NK cells, were evaluated in patients with chronic lymphocytic leukemia (CLL). Patients and Methods: 24 CLL patients and 19 healthy controls were enrolled. Fresh peripheral blood was collected from all subjects and stained with fluorochrome-conjugated antibodies. The frequency of CD56+/CD3–/NKp30+ and CD56+/CD3–/Tim-3+ cells was determined by multicolor flow cytometry. Results: Our results revealed that Tim-3 is significantly upregulated on natural killer (NK) cells of CLL patients in comparison to healthy controls. NK cells of CLL patients showed lower expression of NKp30-activating receptor compared to controls. Tim-3 expression pattern on NK cells of CLL patients was correlated with poor prognostic factors including low hemoglobin level, high absolute lymphocyte count, and high serum C-reactive protein level. Conclusion: Dysregulated expression of Tim-3 and NKp30 receptors confirms the exhaustion state of NK cells in CLL. Our data introduce Tim-3 as a promising biomarker and potential target for immunotherapy of CLL.

Gastric cancer is a major cause of cancer mortality worldwide, with a low survival rate for patients with advanced forms of the disease. Over the recent decades, the investigation of the pathophysiological mechanisms of tumourigenesis has opened promising avenues to understand some of the complexities of cancer treatment. However, tumour regeneration and metastasis impose great difficulty for gastric cancer cure. In recent years, cancer stem cells -a small subset of tumour cells in many cancers -have become a major focus of cancer research. Cancer stem cells are capable of selfrenewal and are known to be responsible for tumour initiation, metastasis, therapy resistance and cancer recurrence. Recent studies have revealed the key role of microRNAs -small noncoding RNAs regulating gene expression -in these processes. MicroRNAs play crucial roles in the regulation of a wide range of biological processes in a post-transcriptional manner, though their expression is dysregulated in most malignancies, including gastric cancer. In this article, we review the consequences of aberrant expression of microRNA-34 in cancer and cancer stem cells, with a specific focus on the miR-34 dysregulation in gastric cancer and gastric cancer stem cells. We address the critical effects of the aberrant expression of miR-34 and its target genes in maintaining cancer stem cell properties. Information collection and discussion about the advancements in gastric cancer stem cells and microRNAs can be useful for providing novel insights into patient treatment.

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