Reprogramming the tumor immune microenvironment using engineered dual-drug loaded Salmonella.

Synergistic combinations of immunotherapeutic agents can improve the performance of anti-cancer therapies but may lead to immune-mediated adverse effects. These side-effects can be overcome by using a tumor-specific delivery system. Here, we report a method of targeted immunotherapy using an attenuated Salmonella typhimurium (SAM-FC) engineered to release dual payloads: cytolysin A (ClyA), a cytolytic anti-cancer agent, and Vibrio vulnificus flagellin B (FlaB), a potent inducer of anti-tumor innate immunity. Localized secretion of ClyA from SAM-FC induces immunogenic cancer cell death and promotes release of tumor-specific antigens and damage-associated molecular patterns, which establish long-term antitumor memory. Localized secretion of FlaB promotes phenotypic and functional remodeling of intratumoral macrophages that markedly inhibits tumor metastasis in mice bearing tumors of mouse and human origin. Both primary and metastatic tumors from bacteria-treated female mice are characterized by massive infiltration of anti-tumorigenic innate immune cells and activated tumor-specific effector/memory T cells; however, the percentage of immunosuppressive cells is low. Here, we show that SAM-FC induces functional reprogramming of the tumor immune microenvironment by activating both the innate and adaptive arms of the immune system and can be used for targeted delivery of multiple immunotherapeutic payloads for the establishment of potent and long-lasting antitumor immunity.

Toxic metals in rice among Asian countries: A review of occurrence and potential human health risks.

Heavy metals such as cadmium (Cd), arsenic (As), and lead (Pb) pose significant health risks, particularly in Asia, where rice is a staple for nearly three billion people. Despite their known dangers and environmental prevalence, studies addressing their concentrations in rice across different regions and the associated health implications remain insufficient. This review systematically examines the occurrence and impact of these toxic elements, filling a critical gap in the literature. Data from seven countries indicate mean concentrations in the order of Pb > As>Cd, with values of 0.255 ± 0.013, 0.236 ± 0.317, and 0.136 ± 0.150 mg/kg, respectively. Uncertainty analysis shows extensive variability, especially for Cd, with a 95% confidence interval range from 0.220 to 0.992 mg/kg. The typical daily intake of heavy metals through rice consumption, in the order of As>Cd > Pb, frequently exceeds safe limits. Generally, data obtained from various studies showed that children were more prone to heavy metal contamination through rice consumption than adults. This review is fundamental for ongoing monitoring, future research, and management strategies to reduce heavy metal contamination in rice.