Electrostimulus Associated PD-L1 Expression on Cell Membrane Revealed by Immune SERS Nanoprobes

Programmed cell death ligand 1 (PD-L1) is considered a major immune checkpoint protein that mediates antitumor immune suppression and response. Effectively regulating PD-L1 expression and dynamic monitoring for immunotherapy has...

Checkpoint protein expression in the tumor microenvironment defines the outcome of classical Hodgkin lymphoma patients

Emerging evidence indicates a major impact for the tumor microenvironment (TME) and immune escape in the pathogenesis and clinical course of classical Hodgkin lymphoma (cHL). We used gene expression profiling (n=88), CIBERSORT, and multiplex immunohistochemistry (n=131) to characterize the immunoprofile of cHL TME, and correlated the findings with survival. Gene expression analysis divided tumors into subgroups with T cell-inflamed and non-inflamed TME. Several macrophage-related genes were upregulated in samples with the non-T cell-inflamed TME, and based on the immune cell proportions, the samples clustered according to the content of T cells and macrophages. A cluster with high proportions of checkpoint protein (PD-1, PD-L1, IDO-1, LAG-3, and TIM-3) positive immune cells translated to unfavorable overall survival (OS) (5-year OS 76% vs. 96%, P=0.010), and remained as an independent prognostic factor for OS in multivariable analysis (HR 4.34, 95% CI 1.05-17.91, P=0.043). cHLs with high proportions of checkpoint proteins overexpressed genes coding for cytolytic factors, proposing paradoxically that they were immunologically active. This checkpoint molecule gene signature translated to inferior survival in a validation cohort of 290 diagnostic cHL samples (P<0.001) and in an expansion cohort of 84 cHL relapse samples (P=0.048). Our findings demonstrate the impact of T cell- and macrophage-mediated checkpoint system on the survival of patients with cHL.

A Novel Renoprotective Strategy: Upregulation of PD-L1 Mitigates Cisplatin-Induced Acute Kidney Injury

The innate and adaptive immunities have been documented to participate in the pathogenesis of nephrotoxic acute kidney injury (AKI); however, the mechanisms controlling these processes have yet to be established. In our cisplatin-induced AKI mouse model, we show pathological damage to the kidneys, with the classical markers elevated, consistent with the response to cisplatin treatment. Through assessments of the components of the immune system, both locally and globally, we demonstrate that the immune microenvironment of injured kidneys was associated with an increased infiltration of CD4+ T cells and macrophages concomitant with decreased Treg cell populations. Our cell-based assays and animal studies further show that cisplatin exposure downregulated the protein levels of programmed death-ligand 1 (PD-L1), an immune checkpoint protein, in primary renal proximal tubular epithelial cells, and that these inhibitions were dose-dependent. After orthotopic delivery of PD-L1 gene into the kidneys, cisplatin-exposed mice displayed lower levels of both serum urea nitrogen and creatinine upon PD-L1 expression. Our data suggest a renoprotective effect of the immune checkpoint protein, and thereby provide a novel therapeutic strategy for cisplatin-induced AKI.