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Nivolumab is Food and Drug Administration approved in sorafenib-experienced, advanced hepatocellular carcinoma (HCC). Post-registration data of treatment in a real-world setting is lacking.

We performed an international, multicenter observational study to confirm safety and efficacy of nivolumab in 233 patients treated outside clinical trials from eight centers in North America, Europe and Asia.

Patients received nivolumab for Barcelona Clinic Liver Cancer stage C (n

191, 92.0%) and Child-Pugh (CP) A (n

158, 67.8%) or B (n

75, 32.2%) HCC as first (n

85, 36.5%) or second to fourth systemic therapy line (n

148, 63.5%). Objective response rate (ORR) was 22.4% and disease control rate was 52.1%. Median overall survival (OS) was 12.2 months (95% CI 8.4 to 16.0) and median progression-free survival was 10.1 months (95% CI 6.1 to 14.2). Treatment-related adverse events of grade >2 occurred in 26 patients (11.2%). Efficacy and safety were similar across CP classes and therapy line. OS was shorter in CP-B than A (7.3 months vs 16.3 months, p<0.001) and in post-first line use (10.4 months vs 16.3 months, p

0.05). Achievement of an objective response predicted for improved OS (25.4 months vs 13.2 months, p<0.001).

This study confirms safety and efficacy of nivolumab in advanced HCC across various lines of therapy and degrees of liver dysfunction. Despite equal ORR and toxicity to nivolumab, patients with CP-B functional class have shorter survival than the patients with CP-A.

This study confirms safety and efficacy of nivolumab in advanced HCC across various lines of therapy and degrees of liver dysfunction. Despite equal ORR and toxicity to nivolumab, patients with CP-B functional class have shorter survival than the patients with CP-A.

Many cancer cells express a major histocompatibility complex class I low/ programmed cell death 1 ligand 1 positive (MHC-I

/PD-L1

) cell surface profile. For immunotherapy, there is, thus, an urgent need to restore presentation competence of cancer cells with defects in MHC-I processing/presentation combined with immune interventions that tackle the tumor-initiated PD-L1/PD-1 signaling axis. Using pancreatic ductal adenocarcinoma cells (PDACCs) as a model, we here explored if (and how) expression/processing of tumor antigens via transporters associated with antigen processing (TAP) affects priming of CD8 T cells in PD-1/PD-L1-competent/-deficient mice.

We generated tumor antigen-expressing vectors, immunized TAP-competent/-deficient mice and determined de novo primed CD8 T-cell frequencies by flow cytometry. Similarly, we explored the antigenicity and PD-L1/PD-1 sensitivity of PDACCs versus interferon-γ (IFN-γ)-treated PDACCs in PD-1/PD-L1-competent/deficient mice. The IFN-γ-induced effects on gene and l is attractive for cell-based immunotherapies, because it restores TAP-dependent antigen processing in cancer cells, facilitates priming of TAP-dependent effector CD8 T-cell responses without additional check point inhibitors and could be combined with genetic vaccines that complement priming of TAP-independent CD8 T cells.

The IFN-γ-treatment protocol is attractive for cell-based immunotherapies, because it restores TAP-dependent antigen processing in cancer cells, facilitates priming of TAP-dependent effector CD8 T-cell responses without additional check point inhibitors and could be combined with genetic vaccines that complement priming of TAP-independent CD8 T cells.

The present study aimed to discover novel susceptibility loci associated with risk of rheumatoid arthritis (RA).

We performed a new genome-wide association study (GWAS) in Chinese subjects (1027 RA cases and 2879 controls) and further conducted an expanded meta-analysis with previous GWAS summary data and replication studies. The functional roles of the associated loci were interrogated using publicly available databases. Dual-luciferase reporter and cytokine assay were also used for exploring variant function.

We identified five new susceptibility loci (

,

,

,

and

 ; p

<5.00E-08) with same effect direction in each study cohort. The sensitivity analyses showed that the genetic association of at least three loci was reliable and robust. JTC-801 All these lead variants are expression quantitative trait loci and overlapped with epigenetic marks in immune cells. Furthermore, genes within the five loci are genetically associated with risk of other autoimmune diseases, and genes within four loci are known functional players in autoimmunity, which supports the validity of our findings. The reporter assay showed that the risk allele of rs8030390 in

have significantly increased reporter activity in HEK293T cells. In addition, the cytokine assay found that the risk allele of rs244672 in

was most significantly associated with increased plasma IL-17A levels in healthy controls. Finally, identified likely causal genes in these loci significantly interacted with RA drug targets.

This study identified novel RA risk loci and highlighted that comprehensive genetic study can provide important information for RA pathogenesis and drug therapy.

This study identified novel RA risk loci and highlighted that comprehensive genetic study can provide important information for RA pathogenesis and drug therapy.

The association between chronic inflammatory demyelinating polyneuropathy (CIDP) and diabetes is uncertain despite important diagnostic and management implications.

We retrospectively analysed two European cohorts, totaling 257 patients with 'definite' or 'probable' CIDP, from Serbia and Birmingham, UK.

Diabetes was present at CIDP diagnosis in 25/139 (18%) subjects in the Serbian cohort and in 23/118 (19.5%) in the UK cohort. In both cohorts, diabetes prevalence was higher than local general population prevalence rates (RR 2.09; 95% CI 1.39 to 2.95 and RR 2.22; 95% CI 1.46 to 3.17, respectively). Considering typical CIDP only, diabetes prevalence was greater than expected in both cohorts (RR 2.58; 95% CI 1.60 to 3.82 and RR 2.68; 95% CI 1.71 to 3.87, respectively). CIDP with diabetes occurred later in life than CIDP without diabetes (58.96 years, SD 11.09 vs 51.71 years, SD 16.02; p=0.003) and presented more frequently in the typical form than in patients without diabetes (79.2% vs 61.2%; p=0.02). Baseline Inflammatory Neuropathy Cause and Treatment disability scores were similar in patients with and without diabetes (p=0.