Myeloid-derived suppressor cells (MDSCs) play crucial roles in tumorigenesis and their inhibition is critical for successful cancer immunotherapy. MDSCs undergo metabolic reprogramming from glycolysis to fatty acid oxidation (FAO) and oxidative phosphorylation led by lipid accumulation in tumor. Increased exogenous fatty acid uptake by tumor MDSCs enhance their immunosuppressive activity on T-cells thus promoting tumor progression. Tumor-infiltrating MDSCs in mice may prefer FAO over glycolysis as a primary source of energy while treatment with FAO inhibitors improved anti-tumor immunity. This review highlights the immunosuppressive functions of lipid metabolism and its signaling pathways on MDSCs in the tumor microenvironment. The manipulation of these pathways in MDSCs is relevant to understand the tumor microenvironment therefore, could provide novel therapeutic approaches to enhance cancer immunotherapy.

Summary: Natural killer cells are potent cytotoxic lymphocytes specialized in recognizing and eliminating transformed cells, and in orchestrating adaptive anti‐tumour immunity. However, NK cells are usually functionally exhausted in the tumour microenvironment. Strategies such as checkpoint blockades are under investigation to overcome NK cell exhaustion in order to boost anti‐tumour immunity. The discovery and development of the CRISPR/Cas9 technology offer a flexible and efficient gene‐editing capability in modulating various pathways that mediate NK cell exhaustion, and in arming NK cells with novel chimeric antigen receptors to specifically target tumour cells. Despite the high efficiency in its gene‐editing capability, difficulty in the delivery of the CRISPR/Cas9 system remains a major bottleneck for its therapeutic applications, particularly for NK cells. The current review discusses feasible approaches to deliver the CRISPR/Cas9 systems, as well as potential strategies in gene‐editing for NK cell immunotherapy for cancers.

Introduction: Cancer is a major public health problem and a global leading cause of death where the screening, diagnosis, prediction, survival estimation, and treatment of cancer and control measures are still a major challenge. The rise of Artificial Intelligence (AI) and Machine Learning (ML) techniques and their applications in various fields have brought immense value in providing insights into advancement in support of cancer control. Methods: A systematic and thematic analysis was performed on the Scopus database to identify the top 100 cited articles in cancer research. Data were analyzed using RStudio and VOSviewer.Var1.6.6. Results: The top 100 articles in AI and ML in cancer received a 33 920 citation score with a range of 108 to 5758 times. Doi Kunio from the USA was the most cited author with total number of citations (TNC = 663). Out of 43 contributed countries, 30% of the top 100 cited articles originated from the USA, and 10% originated from China. Among the 57 peer-reviewed journals, the “Expert Systems with Application” published 8% of the total articles. The results were presented in highlight technological advancement through AI and ML via the widespread use of Artificial Neural Network (ANNs), Deep Learning or machine learning techniques, Mammography-based Model, Convolutional Neural Networks (SC-CNN), and text mining techniques in the prediction, diagnosis, and prevention of various types of cancers towards cancer control. Conclusions: This bibliometric study provides detailed overview of the most cited empirical evidence in AI and ML adoption in cancer research that could efficiently help in designing future research. The innovations guarantee greater speed by using AI and ML in the detection and control of cancer to improve patient experience.

Neurodegenerative diseases (NDs) are a diverse group of disorders characterized by the progressive degeneration of the structure and function of the central or peripheral nervous systems. One of the major features of NDs, such as Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD), is the aggregation of specific misfolded proteins, which induces cellular dysfunction, neuronal death, loss of synaptic connections and eventually brain damage. By far, a great amount of evidence has suggested that TRIM family proteins play crucial roles in the turnover of normal regulatory and misfolded proteins. To maintain cellular protein quality control, cells rely on two major classes of proteostasis: molecular chaperones and the degradative systems, the latter includes the ubiquitin-proteasome system (UPS) and autophagy; and their dysfunction has been established to result in various physiological disorders including NDs. Emerging evidence has shown that TRIM proteins are key players in facilitating the clearance of misfolded protein aggregates associated with neurodegenerative disorders. Understanding the different pathways these TRIM proteins employ during episodes of neurodegenerative disorder represents a promising therapeutic target. In this review, we elucidated and summarized the diverse roles with underlying mechanisms of members of the TRIM family proteins in NDs.

The discovery of clustered regularly interspaced short palindromic repeats and CRISPR‐associated protein 9 (CRISPR‐Cas9) technology has brought advances in the genetic manipulation of eukaryotic cells, which has revolutionised cancer research and treatment options. It is increasingly being used in cancer immunotherapy, including adoptive T and natural killer (NK) cell transfer, secretion of antibodies, cytokine stimulation and overcoming immune checkpoints. CRISPR‐Cas9 technology is used in autologous T cells and NK cells to express various innovative antigen designs and combinations of chimeric antigen receptors (CARs) targeted at specific antigens for haematological and solid tumors. Additionally, advanced engineering in immune cells to enhance their sensing circuits with sophisticated functionality is now possible. Intensive research on the CRISPR‐Cas9 system has provided scientists with the ability to overcome the hostile tumor microenvironment and generate more products for future clinical use, especially off‐the‐shelf, universal cellular products, bringing exciting milestones for immunotherapy. This review discussed the application and challenges of CRISPR technology in cancer research and immunotherapy, its advances and prospects for promoting new cell‐based therapeutic beyond immune oncology.

Natural Killer (NK) cells are components of innate immune surveillance against transformed cells. NK cell immunotherapy has attracted attention as a promising strategy for cancer treatment, whose antitumor effects, however, require further improvement. The use of small molecules with immunomodulatory potentials and selective tumor-killing possesses the potential to complement immunotherapy. This study demonstrated that Piperlongumine (PL), a natural alkaloid obtained from long pepper fruit, alone has antitumor and anti-proliferative potential on all the tested tumors in vitro. PL pretreatment of tumor cells also potentiates their susceptibility to NK cell cytolysis at the doses where NK cell functions were preserved. Importantly, PL suppresses both NK -sensitive MHC-I -deficient and MHC-I -sufficient tumor growth in vivo. Mechanistically, PL induces misfolded proteins, impedes autophagy, increases ROS and tumor conjugation with NK cells. Furthermore, PL enhances the expression of NK cell-activating receptors on NK cells and its ligands on tumor cells, possibly leading to increased susceptibility to NK cell killing. Our findings showed the antitumor and immunomodulatory potential of PL, which could be explored to complement NK cell immunotherapy for cancer treatment.