Notes

Species-specific regulation of inbuilt immunity through nutritional Deborah signaling.
ity justifying further investigation of this treatment in an unselected population of patients with rGB.Cerebral edema following chimeric antigen receptor (CAR) T-cell therapy can be fatal. ZUMA-2 is a pivotal phase 2, multicenter study evaluating KTE-X19, an autologous anti-CD19 CAR T-cell therapy, in relapsed/refractory mantle cell lymphoma. We describe a 65-year-old patient in ZUMA-2 who developed cerebral edema following CAR T-cell therapy and had complete recovery after multimodality clinical intervention including rabbit antithymocyte globulin (ATG). Biomarker results show early and robust CAR T-cell expansion and related induction of inflammatory cytokines, followed by rapid declines in CAR T-cell and proinflammatory cytokine levels after ATG administration. This clinical profile highlights a potential relevance of ATG in treating severe CAR T-cell-related neurotoxicity.
Natural killer (NK) cells play a crucial role in tumor immunosurveillance through their cytotoxic effector functions and their capacity to interact with other immune cells to build a coordinated antitumor immune response. Emerging data reveal NK cell dysfunction within the tumor microenvironment (TME) through checkpoint inhibitory molecules associated with a regulatory phenotype.

We aimed at analyzing the gene expression profile of intratumoral NK cells compared with non-tumorous NK cells, and to characterize their inhibitory function in the TME.

NK cells were sorted from human lung tumor tissue and compared with non- tumoral distant lungs.

In the current study, we identify a unique gene signature of NK cell dysfunction in human non-small cell lung carcinoma (NSCLC). First, transcriptomic analysis reveals significant changes related to migratory pattern with a downregulation of sphingosine-1-phosphate receptor 1 (S1PR1) and CX3C chemokine receptor 1 (CX3CR1) and overexpression of C-X-C chemokine receptor type 5 (CXCR5) and C-X-C chemokine receptor type 6 (CXCR6). Second, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and killer cell lectin like receptor (KLRC1) inhibitory molecules were increased in intratumoral NK cells, and CTLA-4 blockade could partially restore MHC class II level on dendritic cell (DC) that was impaired during the DCs/NK cell cross talk. Finally, NK cell density impacts the positive prognostic value of CD8
T cells in NSCLC.

These findings demonstrate novel molecular cues associated with NK cell inhibitory functions in NSCLC.
These findings demonstrate novel molecular cues associated with NK cell inhibitory functions in NSCLC.In the evolving immune-oncology landscape, numerous patients with cancer are constantly treated with immune checkpoint inhibitors (ICPIs) but among them, only sporadic cases with pre-existing hepatitis B virus (HBV) and hepatitis C virus (HCV) are recorded. selleck inhibitor Despite the global dissemination of HBV and HCV infections, viral hepatitis-infected patients with cancer were traditionally excluded from ICPIs containing trials and current evidence is particularly limited in case reports, retrospective cohort studies and in few clinical trials on advanced hepatocellular carcinoma. Thus, many concerns still remain about the overall oncological management of this special subpopulation, including questions about the efficacy, toxicity and reactivation risks induced by ICPIs. Here, we examine the natural course of both HBV and HCV in cancer environment, review the latest antiviral guidelines for patients undergoing systematic cancer therapies, estimating treatment-related immunosuppression and relocate immunotherapy in this onset of immunotherapy should be suggested as a reasonable and maybe cost-effective strategy but the decision to administer ICPIs and the necessity of prophylaxis should always be weighed at a multidisciplinary level and be individualized in each case, up to be established by future clinical trials.Shortages of life-saving medical resources caused by COVID-19 have prompted hospitals, healthcare systems, and governmentsto develop crisis standards of care, including 'triage protocols' to potentially ration medical supplies during the public health emergency. At the same time, the pandemic has highlighted and exacerbated racial, ethnic, and socioeconomic health disparities that together constitute a form of structural racism. These disparities pose a critical ethical challenge in developing fair triage systems that will maximize lives saved without perpetuating systemic inequities. Here we review alternatives to 'utilitarian' triage, including first-come first-served, egalitarian, and prioritarian systems of allocating scarce medical resources. We assess the comparative advantages and disadvantages of these allocation schemes. Ultimately, we argue that while triage protocols should not exacerbate disparities, they are not an adequate mechanism for redressing systemic health inequities. Entrenched health disparities must be addressed through broader social change.Diabetic kidney disease (DKD) remains the most common cause of kidney failure, and the treatment options are insufficient. Here, we used a connectivity mapping approach to first collect 15 gene expression signatures from 11 DKD-related published independent studies. Then, by querying the Library of Integrated Network-based Cellular Signatures (LINCS) L1000 data set, we identified drugs and other bioactive small molecules that are predicted to reverse these gene signatures in the diabetic kidney. Among the top consensus candidates, we selected a PLK1 inhibitor (BI-2536) for further experimental validation. We found that PLK1 expression was increased in the glomeruli of both human and mouse diabetic kidneys and localized largely in mesangial cells. We also found that BI-2536 inhibited mesangial cell proliferation and extracellular matrix in vitro and ameliorated proteinuria and kidney injury in DKD mice. Further pathway analysis of the genes predicted to be reversed by the PLK1 inhibitor was of members of the TNF-α/NF-κB, JAK/STAT, and TGF-β/Smad3 pathways. In vitro, either BI-2536 treatment or knockdown of PLK1 dampened the NF-κB and Smad3 signal transduction and transcriptional activation. Together, these results suggest that the PLK1 inhibitor BI-2536 should be further investigated as a novel therapy for DKD.
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