Research progress and clinical prospect of immunocytotherapy for the treatment of hepatocellular carcinoma. International immunopharmacology As a common malignant tumor, hepatocellular carcinoma (HCC) has high fatality rate due to its strong metastasis and high degree of malignancy. Current treatment strategies adopted in clinical practice were still conventional surgery, assisted with interventional therapy, radiotherapy and chemotherapy. However these treatments have limited effects with high recurrence rate. Current research progress of immunocytotherapy has shown that tumor cells can be directly identified and killed by stimulating the immune function and enhancing the anti-tumor immunity in tumor microenvironment. Targeted immunotherapeutics have therefore become the hope of conquering cancer in the future. It can kill tumor cells without damaging the body's immune system and function, restore and strengthen the body's natural anti-tumor immune system. It can reduce the toxic side effects of radiotherapy and chemotherapy, reduce the recurrence rate and prolong the survival period of patients with HCC. Currently, the immune cells widely studied are mainly as follows: Dendritic cells (DC), Cytokine-induced killer (CIK), DC-CIK, Chimeric antigen receptor T cells (CAR-T), Tumor infiltrating lymphocyte (TIL) and Natural killer cell (NK). Immunocytotherapy is a long-term treatment method, some studies have combined traditional therapy with immunocytotherapy and achieved significant effects, providing experimental basis for the application of immunocytotherapy. However, there are still some difficulties in the clinical application of immune cells. In this article, we discuss the application of immunocytotherapy in the clinical treatment of HCC, their effectiveness either alone or in combination with conventional therapies, and how future immunocytotherapeutics can be further improved from investigations in tumour immunology. 10.1016/j.intimp.2020.106351

ACSM1 and ACSM3 Regulate Fatty Acid Metabolism to Support Prostate Cancer Growth and Constrain Ferroptosis. Cancer research Solid tumors are highly reliant on lipids for energy, growth, and survival. In prostate cancer, the activity of the androgen receptor (AR) is associated with reprogramming of lipid metabolic processes. Here, we identified acyl-CoA synthetase medium chain family members 1 and 3 (ACSM1 and ACSM3) as AR-regulated mediators of prostate cancer metabolism and growth. ACSM1 and ACSM3 were upregulated in prostate tumors compared with nonmalignant tissues and other cancer types. Both enzymes enhanced proliferation and protected prostate cancer cells from death in vitro, whereas silencing ACSM3 led to reduced tumor growth in an orthotopic xenograft model. ACSM1 and ACSM3 were major regulators of the prostate cancer lipidome and enhanced energy production via fatty acid oxidation. Metabolic dysregulation caused by loss of ACSM1/3 led to mitochondrial oxidative stress, lipid peroxidation, and cell death by ferroptosis. Conversely, elevated ACSM1/3 activity enabled prostate cancer cells to survive toxic levels of medium chain fatty acids and promoted resistance to ferroptosis-inducing drugs and AR antagonists. Collectively, this study reveals a tumor-promoting function of medium chain acyl-CoA synthetases and positions ACSM1 and ACSM3 as key players in prostate cancer progression and therapy resistance. Significance: Androgen receptor-induced ACSM1 and ACSM3 mediate a metabolic pathway in prostate cancer that enables the utilization of medium chain fatty acids for energy production, blocks ferroptosis, and drives resistance to clinically approved antiandrogens. 10.1158/0008-5472.CAN-23-1489

Friend or foe? Deciphering androgen receptor action to improve bipolar androgen therapy for prostate cancer. Endocrine-related cancer Inhibiting the activity of the androgen receptor (AR) is the cornerstone treatment for advanced prostate cancer. AR-targeted therapies are highly effective in slowing disease progression but are not curative. Failure of these therapies results in a disease state termed castration-resistant prostate cancer, which is associated with significant patient morbidity and mortality. In most cases, resistance to AR-targeted therapies arises due to alterations that reactivate the AR signalling axis. Interestingly, it has long been recognised that potent activation of AR with supraphysiological levels of androgens can suppress prostate cancer growth in both preclinical models and patients. This intriguing paradox, where both inhibition and activation of AR have anti-cancer effects, is now being harnessed clinically in the form of bipolar androgen therapy (BAT). This review describes mechanisms underlying the tumour-suppressive functions of AR in the context of potent androgenic stimulation and discusses how our maturing understanding of these processes is influencing the clinical deployment of BAT. 10.1530/ERC-24-0208