Pancreatic cancer has the worst prognosis among all cancers. Cancer screening of body fluids may improve the survival time prognosis of patients, who are often diagnosed too late at an incurable stage. Several studies report the dysregulation of lipid metabolism in tumor cells, suggesting that changes in the blood lipidome may accompany tumor growth. Here we show that the comprehensive mass spectrometric determination of a wide range of serum lipids reveals statistically significant differences between pancreatic cancer patients and healthy controls, as visualized by multivariate data analysis. Three phases of biomarker discovery research (discovery, qualification, and verification) are applied for 830 samples in total, which shows the dysregulation of some very long chain sphingomyelins, ceramides, and (lyso)phosphatidylcholines. The sensitivity and specificity to diagnose pancreatic cancer are over 90%, which outperforms CA 19-9, especially at an early stage, and is comparable to established diagnostic imaging methods. Furthermore, selected lipid species indicate a potential as prognostic biomarkers.

Background: Serum neurofilament light chain (sNfL) is a marker of neuroaxonal injury. There is a lack of studies investigating the dynamics of relationships between sNfL levels and radiological disease activity over long-term follow-up in multiple sclerosis (MS). Objectives: To investigate the relationship among repeated measures of sNfL, lesion burden accumulation, brain volume loss and clinical measures. Methods: We investigated 172 patients in the early stages of MS (McDonald 2017 criteria). Clinical exams were performed every 3 months and brain magnetic resonance imaging (MRI) scans were collected annually over 48 months. sNfL levels were measured in serum by Simoa assay at the time of treatment initiation and then annually over 36 months. Results: In repeated-measures analysis, considering all time points, we found a strong relationship between percentage changes of sNfL and lesion burden accumulation assessed by T1 lesion volume ( p < 0.001) and T2 lesion number ( p < 0.001). There was no relationship between percentage changes of sNfL and brain volume loss over 36 months ( p > 0.1). Early sNfL levels were associated with delayed brain volume loss after 48 months ( p < 0.001). Patients with No Evidence of Disease Activity (NEDA-3) status showed lower sNfL levels compared with active MS patients. Conclusions: sNfL is associated with ongoing neuroinflammation and predictive of future neurodegeneration in early MS.

Purpose: The successful implementation of immune checkpoint inhibitors (ICIs) in the clinical management of various solid tumors has raised considerable expectations for patients with epithelial ovarian carcinoma (EOC). However, EOC is poorly responsive to ICIs due to immunological features including limited tumor mutational burden (TMB) and poor lymphocytic infiltration. An autologous dendritic cell (DC)-based vaccine (DCVAC) has recently been shown to be safe and to significantly improve progression-free survival (PFS) in a randomized Phase II clinical trial enrolling patients with EOC (SOV01, NCT02107937). Experimental design: We harnessed sequencing, flow cytometry, multispectral immunofluorescence microscopy, immunohistochemistry to analyze (pre-treatment) tumor and (pre-treatment and post-treatment) peripheral blood samples from 82 patients enrolled in SOV01, with the aim of identifying immunological biomarkers that would improve the clinical management of patients with EOC treated with DCVAC. Results: Although higher-than-median TMB and abundant CD8+ T cell infiltration were associated with superior clinical benefits in patients with EOC receiving standard-of-care chemotherapy, the same did not hold true in women receiving DCVAC. Conversely, superior clinical responses to DCVAC were observed in patients with lower-than-median TMB and scarce CD8+ T cell infiltration. Such responses were accompanied by signs of improved effector functions and tumor-specific cytotoxicity in the peripheral blood. Conclusions: Our findings suggest that while patients with highly infiltrated, "hot" EOCs benefit from chemotherapy, women with "cold" EOCs may instead require DC-based vaccination to jumpstart clinically relevant anticancer immune responses.

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