Goldberg, L. | Search bioRxiv

bioRxiv2025

Immunometabolic determinants of long-term response in leukemia patients receiving CD19 CAR T cell therapy

Although most patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) receiving CD19-targeted chimeric antigen receptor (CAR) T cell therapy achieve remission, loss of CAR T cell functionality and subsequent relapse remains an unmet therapeutic need. We applied an integrative approach to study the immunometabolism of pre- and post-infusion CD19-CAR T cells of patients with relapsed/refractory B-ALL. Pre-infusion CAR T cells of long-term responders (LTR) had increased oxidative phosphorylation, fatty acid oxidation, and pentose phosphate pathway activities, higher mitochondrial mass, tighter cristae, and lower mTOR expression compared to products of short-term responders. Post-infusion CAR T cells in bone marrow (BM) of LTR had high immunometabolic plasticity and mTOR-pS6 expression supported by the BM microenvironment. Transient inhibition of mTOR during manufacture induced metabolic reprogramming and enhanced anti-tumor activity of CAR T cells. Our findings provide insight into immunometabolic determinants of long-term response and suggest a therapeutic strategy to improve long-term remission.

immunology↗

bioRxiv2020

Future carbon emissions from global mangrove forest loss

Mangroves have among the highest carbon densities of any tropical forest. These "blue carbon" ecosystems can store large amounts of carbon for long periods, and their protection reduces greenhouse gas emissions and supports climate change mitigation. The incorporation of mangroves into Nationally Determined Contributions to the Paris Agreement and their valuation on carbon markets requires predicting how the management of different land-uses can prevent future greenhouse gas emissions and increase CO2 sequestration. Management actions can reduce CO2 emissions and enhance sequestration, but should be guided by predictions of future emissions, not just carbon storage. We project emissions and forgone soil carbon sequestration potential caused by mangrove loss with comprehensive global datasets for carbon stocks, mangrove distribution, deforestation rates, and drivers of land-use change. Emissions from mangrove loss could reach 2,397 Tg CO2eq by the end of the century, or 3,401 Tg CO2eq when considering forgone carbon sequestration. The highest emissions were predicted in southeast and south Asia (West Coral Triangle, Sunda Shelf, and the Bay of Bengal) due to conversion to aquaculture or agriculture, followed by the Caribbean (Tropical Northwest Atlantic) due to clearing and erosion, and the Andaman coast (West Myanmar) and north Brazil due to erosion. Together, these six regions accounted for 90% of the total potential CO2eq future emissions. We highlight hotspots for future emissions and the land-use specfic management actions that could avoid them with appropriate policies and regulation.

biochemistry↗