Hypothermic Perfusion Modifies the Association Between Anti-LG3 Antibodies and Delayed Graft Function in Kidney Recipients.

We previously reported associations between autoantibodies to the LG3 fragment of perlecan, anti-LG3, and a higher risk of delayed graft function (DGF) in kidney transplant recipients. Here, we aimed to determine whether some factors that modulate ischemia-reperfusion injury (IRI) can modify this association. We performed a retrospective cohort study in kidney transplant recipients in 2 university-affiliated centers. In 687 patients, we show that high pre-transplant anti-LG3 are associated with DGF when the kidney is transported on ice (odds ratio (OR): 1.75, 95% confidence interval 1.02-3.00), but not when placed on hypothermic perfusion pump (OR: 0.78, 95% CI 0.43-1.37). In patients with DGF, high pre-transplant anti-LG3 are associated with a higher risk of graft failure (subdistribution hazard ratio (SHR): 4.07, 95% CI: 1.80, 9.22), while this was not the case in patients with immediate graft function (SHR: 0.50, 95% CI 0.19, 1.29). High anti-LG3 levels are associated with a higher risk of DGF in kidneys exposed to cold storage, but not when hypothermic pump perfusion is used. High anti-LG3 are also associated with a higher risk of graft failure in patients who experience DGF, a clinical manifestation of severe IRI.

Involvement of neuronal factors in tumor angiogenesis and the shaping of the cancer microenvironment.

Emerging evidence suggests that nerves within the tumor microenvironment play a crucial role in regulating angiogenesis. Neurotransmitters and neuropeptides released by nerves can interact with nearby blood vessels and tumor cells, influencing their behavior and modulating the angiogenic response. Moreover, nerve-derived signals may activate signaling pathways that enhance the production of pro-angiogenic factors within the tumor microenvironment, further supporting blood vessel growth around tumors. The intricate network of communication between neural constituents and the vascular system accentuates the potential of therapeutically targeting neural-mediated pathways as an innovative strategy to modulate tumor angiogenesis and, consequently, neoplastic proliferation. Hereby, we review studies that evaluate the precise molecular interplay and the potential clinical ramifications of manipulating neural elements for the purpose of anti-angiogenic therapeutics within the scope of cancer treatment.