Myeloid-derived suppressor cells as cellular immunotherapy in transplantation and autoimmune diseases.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells, which have been characterized for their immunosuppressive capacity through multiple mechanisms. These cells have been extensively studied in the field of tumor immunity. Emerging evidence has highlighted its essential role in maintaining immune tolerance in transplantation and autoimmunity. Because of their robust immune inhibitory activities, there has been growing interest in MDSC-based cellular therapy. Various pre-clinical studies have demonstrated that the adoptive transfer of MDCS represented a promising therapeutic strategy for immune-related disorders. In this review, we summarize relevant studies of MDSC-based cell therapy in transplantation and autoimmune diseases and discuss the challenges and future directions for clinical application of MDSC-based cell therapy.

Lung adenocarcinoma in a patient with Lynch syndrome: a case report and literature review.

This article presents a case of a 62-year-old Vietnamese woman with a history of Lynch syndrome (LS), who developed lung adenocarcinoma with EGFR L858R mutation. LS is an autosomal dominant cancer predisposition syndrome caused by a pathogenic germline variant in DNA mismatch repair genes, often leading to microsatellite instability. While LS is primarily associated with gastrointestinal, endometrial, ovarian, and urologic tract cancers, lung cancer accounts for less than 1% of LS-related cancers, with only six cases of LS-related lung cancer previously reported in the literature. The patient underwent multiple lines of treatment for her lung adenocarcinoma, including tyrosine kinase inhibitors, stereotactic body radiation therapy, pemetrexed and pembrolizumab, amivantamab, and fam-trastuzumab deruxtecan, but all resulted in only a partial response followed by a progressive disease. This case highlights the complex interplay of genetic cancer predisposition syndromes and the development of spontaneous driver mutations in the disease course and the subsequent management of tumors arising in these patients.

LILRB3 Modulates Acute Myeloid Leukemia Progression and Acts as an Effective Target for CAR T-cell Therapy.

Identifying novel cell surface receptors that regulate leukemia cell differentiation and can be targeted to inhibit cellular proliferation is crucial to improve current treatment modalities in acute myeloid leukemia (AML), especially for relapsed or chemotherapy-refractory leukemia. Leukocyte immunoglobulin-like receptor type B (LILRB) is an immunomodulatory receptor originally found to be expressed in myeloid cells. In this study, we found that LILRB receptors can be induced under inflammatory stimuli and chemotherapy treatment conditions. Blockade of LILRB3 inhibited leukemia cell proliferation and leukemia progression. In addition, treatment with LILRB3 blocking antibodies upregulated myeloid lineage differentiation transcription factors, including PU.1, C/EBP family, and IRF, whereas phosphorylation of proliferation regulators, for example, AKT, cyclin D1, and retinoblastoma protein, was decreased. Conversely, transcriptomic analysis showed LILRB3 activation by agonist antibodies may enhance leukemia survival through upregulation of cholesterol metabolism, which has been shown to promote leukemia cell survival. Moreover, LILRB3-targeted CAR T cells exhibited potent antitumor effects both in vitro and in vivo. Taken together, our results suggest that LILRB3 is a potentially potent target for multiple treatment modalities in AML. SIGNIFICANCE: LILRB3 regulates differentiation and proliferation in acute myeloid leukemia and can be targeted with monoclonal antibodies and CAR T cells to suppress leukemia growth.

Valorization of farm pond biomass as fertilizer for reducing basin-scale phosphorus losses.

Long-term fertilizer phosphorus (P) inputs are causing phosphorous saturation of agricultural soils globally. The saturation is spreading to the edge-of-the-farm stormwater detention systems (SDSs) from where the legacy P is potentially being released to downstream surface waters. We use site-specific and literature data for P-saturated SDSs, to develop and evaluate the biogeochemical and economic feasibility of a P recycling program that targets both low (LIC, sugarcane) and high intensity cropping (HIC, fresh-produce) systems within a watershed. The focus is to close the P cycle loop to rejuvenate P sink function of SDSs. It involves harvesting and composting the SDS's biomass and it's on-farm use as an organic fertilizer for crops. Results showed that harvesting-composting can conservatively increase the P retention from 50% to 77% for HIC and almost complete treatment for LIC. Beyond potentially increasing yield and improving soil health, compost use can further increase in-field retention of P (and water). Additional costs incurred in harvesting and composting can be offset by the economic value of compost and the reduction in State's expenditure on regional P treatment systems. Treatment costs were $26/kg of P for HIC and $42/kg for LIC, 10 times less than the current state expenditure of $355-$909/kg P using constructed wetlands. We propose an incentivized, payment for services (PS) program, where producers are paid for P recycling. The PS program considers the intensity of cropping systems and their location along the drainage network from headwaters to the outlet, to achieve basin-scale P load reduction. The LIC SDSs recover regional P by passing the public water through them while recycling is implemented at the HIC. The estimated basin-scale P retention with harvest-compost approach was 854 metric tons, 5 times the P that entered the Everglades Protection Area in 2018, at 88%-93% less cost than the State treatment systems.

Nutrient and suspended solids removal from petrochemical wastewater via microalgal biofilm cultivation.

Wastewater derived from petroleum refining currently accounts for 33.6 million barrels per day globally. Few wastewater treatment strategies exist to produce value-added products from petroleum refining wastewater. In this study, mixed culture microalgal biofilm-based treatment of petroleum refining wastewater using rotating algae biofilm reactors (RABRs) was compared with suspended-growth open pond lagoon reactors for removal of nutrients and suspended solids. Triplicate reactors were operated for 12 weeks and were continuously fed with petroleum refining wastewater. Effluent wastewater was monitored for nitrogen, phosphorus, total suspended solids (TSS), and chemical oxygen demand (COD). RABR treatment demonstrated a statistically significant increase in removal of nutrients and suspended solids, and increase in biomass productivity, compared to the open pond lagoon treatment. These trends translate to a greater potential for the production of biomass-based fuels, feed, and fertilizer as value-added products. This study is the first demonstration of the cultivation of mixed culture biofilm microalgae on petroleum refining wastewater for the dual purposes of treatment and biomass production.

Volume reduction outweighs biogeochemical processes in controlling phosphorus treatment in aged detention systems.

Stormwater detention areas (SDAs) play an important role in treating end-of-the-farm runoff in phosphorous (P) limited agroecosystems. Phosphorus transport from the SDAs, including those through subsurface pathways, are not well understood. The prevailing understanding of these systems assumes that biogeochemical processes play the primary treatment role and that subsurface losses can be neglected. Water and P fluxes from a SDA located in a row-crop farm were measured for two years (2009-2011) to assess the SDA's role in reducing downstream P loads. The SDA treated 55% (497kg) and 95% (205kg) of the incoming load during Year 1 (Y1, 09-10) and Year 2 (Y2, 10-11), respectively. These treatment efficiencies were similar to surface water volumetric retention (49% in Y1 and 84% in Y2) and varied primarily with rainfall. Similar water volume and P retentions indicate that volume retention is the main process controlling P loads. A limited role of biogeochemical processes was supported by low to no remaining soil P adsorption capacity due to long-term drainage P input. The fact that outflow P concentrations (Y1=368.3µg L-1, Y2=230.4µg L-1) could be approximated by using a simple mixing of rainfall and drainage P input further confirmed the near inert biogeochemical processes. Subsurface P losses through groundwater were 304kg (27% of inflow P) indicating that they are an important source for downstream P. Including subsurface P losses reduces the treatment efficiency to 35% (from 61%). The aboveground biomass in the SDA contained 42% (240kg) of the average incoming P load suggesting that biomass harvesting could be a cost-effective alternative for reviving the role of biogeochemical processes to enhance P treatment in aged, P-saturated SDAs. The 20-year present economic value of P removal through harvesting was estimated to be $341,000, which if covered through a cost share or a payment for P treatment services program could be a positive outcome for both agriculture and public interests.