Frontiers and future of immunotherapy for pancreatic cancer: from molecular mechanisms to clinical application.

Pancreatic cancer is a highly aggressive malignant tumor, that is becoming increasingly common in recent years. Despite advances in intensive treatment modalities including surgery, radiotherapy, biological therapy, and targeted therapy, the overall survival rate has not significantly improved in patients with pancreatic cancer. This may be attributed to the insidious onset, unknown pathophysiology, and poor prognosis of the disease. It is therefore essential to identify and develop more effective and safer treatments for pancreatic cancer. Tumor immunotherapy is the new and fourth pillar of anti-tumor therapy after surgery, radiotherapy, and chemotherapy. Significant progress has made in the use of immunotherapy for a wide variety of malignant tumors in recent years; a breakthrough has also been made in the treatment of pancreatic cancer. This review describes the advances in immune checkpoint inhibitors, cancer vaccines, adoptive cell therapy, oncolytic virus, and matrix-depletion therapies for the treatment of pancreatic cancer. At the same time, some new potential biomarkers and potential immunotherapy combinations for pancreatic cancer are discussed. The molecular mechanisms of various immunotherapies have also been elucidated, and their clinical applications have been highlighted. The current challenges associated with immunotherapy and proposed strategies that hold promise in overcoming these limitations have also been discussed, with the aim of offering new insights into immunotherapy for pancreatic cancer.

Selenobacteria-mediated Se transformation and uptake involving the unique genetic code.

Selenium (Se) is a crucial micronutrient for human health. Plants are the primary source of Se for humans. Selenium in the soil serves as the primary source of Se for plants. The soil contains high total Se content in large areas in Guangxi, China. However, the available Se is low, hindering Se uptake by plants. Microorganisms play a pivotal role in the activation of Se in the soil, thereby enhancing its uptake by plants. In this study, selenobacteria were isolated from Se-rich soils in Guangxi. Then two selenobacteria strains, YLB1-6 and YLB2-1, representing the highest (30,000 µg/mL) and lowest (10,000 µg/mL) Se tolerance levels among the Se-tolerant bacteria, were selected for subsequent analysis. Although the two selenobacteria exhibited distinct effects, they can significantly transform Se species, resulting in a decrease in the soil residual Se (RES-Se) content while concurrently increasing the available Se (AVA-Se) content. Selenobacteria also enhance the transformation of Se valencies, with a significant increase observed in soluble Se6+ (SOL-Se6+). Additionally, selenobacteria can elevate the pH of acidic soil. Selenobacteria also promote the uptake of Se into plants. After treatment with YLB1-6 and YLB2-1, the Se content in the aboveground part of Chinese flowering cabbage increased by 1.96 times and 1.77 times, respectively, while the Se accumulation in the aboveground part of the plant significantly increased by 104.36% and 81.69%, respectively, compared to the control. Further whole-genome sequencing revealed the genetic difference between the two selenobacteria. Additionally, 46 and 38 candidate genes related to selenium utilization were identified from YLB1-6 and YLB2-1, respectively. This work accelerates our understanding of the potential molecular mechanism of Se biofortification by selenobacteria. It also provides microorganisms and gene targets for improving crop varieties or microorganisms to exploit the rich Se source in soil.