Natural Killer (NK) cells and CD8 + cytotoxic T cells are two types of immune cells that can kill target cells through similar cytotoxic mechanisms. With the remarkable success of chimeric antigen receptor (CAR)-engineered T (CAR-T) cells for treating haematological malignancies, there is a rapid growing interest in developing CAR-engineered NK (CAR-NK) cells for cancer therapy. Compared to CAR-T cells, CAR-NK cells could offer some significant advantages, including: (1) better safety, such as a lack or minimal cytokine release syndrome and neurotoxicity in autologous setting and graft-versus-host disease in allogenic setting, (2) multiple mechanisms for activating cytotoxic activity, and (3) high feasibility for ‘off-the-shelf’ manufacturing. CAR-NK cells could be engineered to target diverse antigens, enhance proliferation and persistence in vivo, increase infiltration into solid tumours, overcome resistant tumour microenvironment, and ultimately achieve an effective anti-tumour response. In this review, we focus on recent progress in genetic engineering and clinical application of CAR-NK cells, and discuss current challenges and future promise of CAR-NK cells as a novel cellular immunotherapy in cancer.

Recently, the inflammatory cytokine IL-6 has been reported as a potent inducer of epithelial-mesenchymal transition (EMT) in breast cancer cells with an epithelial phenotype. Furthermore, EMT induces stem cell features in normal and transformed mammary cells. We explored whether IL-6-induced EMT promoted the generation of breast cancer stem-like cells (BrCSCs) in epithelial-like breast cancer cells, and whether the cytokines EGF and bFGF, analogous to IL-6, per se induced epithelial-mesenchymal transition, resulting in the enrichment of BrCSCs in mammosphere cultures. Herein, we provide evidence that IL-6 is capable of generating CD44+ cells with stem-like properties through induction of the EMT in the epithelial-like T47D breast cancer cells. We also show that mammosphere cultures of epithelial-like breast cancer cells, T47D, MCF7, ZR-75-1 and MDA-MB-453 cells, consistently generated stem-like cancer cells solely as a result of the EGF and bFGF cytokines in the mammosphere media mediating EMT. This finding demonstrated the link between the inflammatory cytokine IL-6 and BrCSCs and identified an important mechanism for the enrichment of BrCSCs in mammosphere cultures. Thus, EMT appears to be a critical mechanism for the induction of cancer cells with stem-like properties, and EMT of non-stem cancer cells could be a source of CSCs.

Radioresistance is a major challenge during the treatment of breast cancer. A further understanding of the mechanisms of radioresistance could provide strategies to address this challenge. In our study, we compared the expression of miR- Breast cancer is the most common cancer in women worldwide. 1 Radiotherapy is an important part of the treatment in most patients receiving breast-conserving surgery and displays significant clinical benefits, such as decreasing the risk of local recurrence and reducing the risk of mortality due to breast cancer. 2 However, for certain subtypes of breast cancer (e.g., basal-like), the local and regional control remains unsatisfactory. A major reason for this failure in treatment may be due to its radioresistance. 3-5 Therefore, understanding the molecular mechanisms involved in the radioresistance of breast tumors may lead to improved clinical outcomes.Autophagy is a cellular process that involves selfdegradation and recycling of macromolecules and cellular organelles. 6,7 It is, in most circumstances, a prosurvival mechanism under stressful conditions. Autophagy has been implicated in a variety of human diseases. [7][8][9] Similar to the situation in normal cells, autophagy is also critical for tumor cells to survive stressful conditions, and thus has been implicated in tumor resistance to chemotherapy and radiotherapy. [10][11][12][13] MicroRNAs (miRNAs) regulate a variety of biological processes, including cell proliferation, differentiation and invasion. 14 Dysregulation of miRNAs has been reported to contribute to cancer, 15,16 and implicated in chemoresistance and radioresistance via modulation of autophagy. 10,13 Such findings are not surprising considering the fact that miRNAs are key regulators of autophagy. 17 The miR-200 family is involved in the self-renewal of cancer stem cells, 18 epithelial-to-mesenchymal transition (EMT) 19,20 and chemosensitivity. 21 Recent studies indicated that miR-200c, the prevailing member of the miR-200 family, 19,20,22,23 could sensitize cancer cells to radiation by targeting TBK1 and VEGF-VEGFR2, despite the unspecified relationship between miR-200c and autophagy. 24,25 The results from our study showed that miR-200c could sensitize breast cancer cells to radiation via a mechanism associated with inhibition of irradiation-induced autophagy.