UNASSIGNED: Despite recent advancements in the treatment of metastatic uveal melanoma (UM), the availability of further treatment options remains limited and the prognosis continues to be poor in many cases. In addition to tebentafusp, immune checkpoint blockade (ICB, PD-1 (+/-) CTLA-4 antibodies) is commonly used for metastatic UM, in particular in HLA-A 02:01-negative patients. However, ICB comes at the cost of potentially severe immune-related adverse events (irAE). Thus, the selection of patient groups that are more likely to benefit from ICB is desirable.
UNASSIGNED: In this analysis, 194 patients with metastatic UM undergoing ICB were included. Patients were recruited from German skin cancer sites and the ADOReg registry. To investigate the association of irAE occurrence with treatment response, progression-free survival (PFS), and overall survival (OS) two cohorts were compared: patients without irAE or grade 1/2 irAE (n=137) and patients with grade 3/4 irAE (n=57).
UNASSIGNED: In the entire population, the median OS was 16.4 months, and the median PFS was 2.8 months. Patients with grade 3/4 irAE showed more favorable survival than patients without or grade 1/2 irAE (p=0.0071). IrAE occurred in 44.7% (87/194), and severe irAE in 29.4% (57/194) of patients. Interestingly, irColitis and irHepatitis were significantly associated with longer OS (p=0.0031 and p=0.011, respectively).
UNASSIGNED: This data may indicate an association between irAE and favorable survival outcomes in patients with metastatic UM undergoing ICB treatment and suggests that a reduced tolerance to tumor antigens could be linked to reduced tolerance to self-antigens.

As Immune checkpoint inhibitors are being expanded for use in gynecologic malignancies, rare immune-related adverse events are more frequently being reported. Here we describe a 63-year-old with Stage IIIB mismatch repair deficient uterine adenocarcinoma who underwent six cycles of carboplatin and paclitaxel with partial response but persistent disease. She was then started on single agent pembrolizumab. After six cycles of pembrolizumab, she developed bilateral vision changes and was diagnosed with posterior scleritis. Pembrolizumab was held and she was treated with oral prednisone, with rapid resolution of symptoms. One month after completion of prednisone, vision changes were again reported and she was restarted on a longer oral prednisone course. She then underwent definitive surgical management consisting of a total laparoscopic hysterectomy and bilateral salpingo-oophorectomy, with final pathology of benign endometrial hyperplasia. She has completed her steroid course without any symptoms. Given her complete pathologic response, she was subsequently placed into surveillance and is currently without evidence of disease. Prompt recognition and treatment of this rare immune-related adverse event led to the prevention of potential permanent, debilitating outcomes.

Recent progress in the treatment of advanced melanoma has led to the improved survival of affected patients. However, novel treatments also lead to considerable and distinct skin toxicity. To further characterize cutaneous adverse events (AE) of systemic treatments, we conducted a single-center retrospective study of biopsy-proven cutaneous adverse events of melanoma treatment over a period of 10 years at the University Hospital of Zurich, Switzerland. In 102 identified patients, 135 individual skin AEs developed. Immune checkpoint blockade (ICB) was causal for 81 skin AEs, and 54 were related to targeted therapies (TT). Recorded types of skin AEs included lichenoid, maculopapular, acneiform, urticarial, panniculitis, folliculitis, psoriasiform, granulomatous, eczematous, and others. The incidence of skin AEs was higher with TT (18.54%) than with ICB (9.64%, p = 0.0029). Most AEs were low-grade, although 19.21% of AEs were common terminology criteria for adverse events (CTCAE) Grades 3 or 4. A large spectrum of skin AEs was documented during treatment of advanced melanoma, and distinct phenotypes were observed, depending on treatment classes. AEs occurred earlier during treatment with TT than with ICB, and distinct types of skin AEs were associated with respective treatment classes. This study comprehensively describes skin AEs occurring during systemic treatment for melanoma at a single center.

UNASSIGNED: This study aimed to investigate the role of ficolin-2 (FCN2) in the development and course of hepatocellular carcinoma (HCC) and to contribute to the evolution of innovative HCC therapeutics.
UNASSIGNED: Oncomine, GEPIA (Gene Expression Profiling Interactive Analysis), TISIDB (Tumor Immune System Interactions and Drug Bank database), UALCAN (University of Alabama at Birmingham Cancer data analysis portal), UCSC (University of California, Santa Cruz), R package, the Kaplan-Meier technique, Cox regression analysis, LinkedOmics, Pearson\'s correlation, and a nomogram were used to investigate the prognostic value of FCN2 in HCC. Co-expressed genes were screened. A protein-protein interaction network was created using the STRING database. Finally, immunohistochemistry was performed to establish the expression of FCN2 in HCC tissues. A pan-cancer study centered on HCC-related molecular analysis was also conducted to look for a link between FCN2 and immune infiltration, immune modulators, and chemokine receptors.
UNASSIGNED: In HCC tissues, the expression of FCN2 was observed to be lower than that in normal tissues. This was connected to the HCC marker alpha-fetoprotein, showing that FCN2 is involved in the development and progression of cancer. FCN2 may act through Staphylococcus aureus infection, lectins, and other pathways. Furthermore, at the immune level, the expression of FCN2 in HCC was associated with some immune cell infiltration, immunomodulators, and chemokine receptors.
UNASSIGNED: FCN2 may be an immune checkpoint inhibitor for HCC, creating a breakthrough in the treatment of HCC.

The immune response is an important part of secondary brain injury following intracerebral hemorrhage (ICH), and is related to neurological deficits and prognosis. The mechanisms underlying the immune response and inflammation are of great significance for brain injury and potential functional restoration; however, the immune-related biomarkers and competing endogenous ribonucleic acid (RNA) (ceRNA) networks in the peripheral blood of ICH patients have not yet been constructed. We collected the peripheral blood from ICH patients and controls to assess their ceRNA profiles using LCHuman ceRNA microarray, and to verify their expression with qRT-PCR. Two-hundred-eleven DElncRNAs and one-hundred-one DEmRNAs were detected in the ceRNA microarray of ICH patients. The results of functional enrichment analysis showed that the immune response was an important part of the pathological process of ICH. Twelve lncRNAs, ten miRNAs, and seven mRNAs were present in our constructed immune-related ceRNA network, combining weighted gene co-expression network analysis (WGCNA). Our study was the first to establish the network of the immune-related ceRNAs derived from WGCNA, and to identify leukemia inhibitory factor (LIF) and B cell lymphoma 2-like 13 (BCL2L13) as pivotal immune-related biomarkers in the peripheral blood of ICH patients, which are likely associated with PI3K-Akt, the MAPK signaling pathway, and oxidative phosphorylation. The MOXD2P-miR-211-3p -LIF and LINC00299-miR-198-BCL2L13 axes were indicated to participate in the immune regulatory mechanism of ICH. The goal of our study was to offer innovative insights into the underlying immune regulatory mechanism and to identify possible immune intervention targets for ICH.

Clear-cell renal cell carcinoma (ccRCC) is one of the most common urological cancers. The tumor microenvironment plays an important role in tumor development. The present study was conducted to identify novel immune-related biomarkers. The differentially expressed genes were identified using the ESTIMATE algorithm base on GEO and TCGA databases. The Kaplan-Meier survival curve and univariate and multivariate analyses were performed. The association between ST8SIA1 and the immune system was explored. The gene set enrichment analysis (GSEA) and online databases were used for functional annotation. ST8SIA1 was identified as a potential prognostic gene. Elevated ST8SIA1 was observed in the tumor tissues compared with adjacent normal tissues and associated with higher T stage and advanced TNM stage (all p < 0.05). The mRNA and protein levels of ST8SIA1 in cancer tissues and cells are also upregulated. The Kaplan-Meier survival curve and univariate and multivariate analyses showed that higher expression of ST8SIA1 was associated with worse OS (all p < 0.05). ST8SIA1 expression levels were negatively correlated with tumor purity and positively associated with infiltrated immune cells and expression of immune checkpoint genes. Function analysis also revealed that ST8SIA1 was significantly associated with immune-related pathways. In conclusion, ST8SIA1 was identified as an immune-related gene and a potential target in ccRCC patients. Further relevant studies are required to validate our findings.

Purpose: Our research developed immune-related long noncoding RNAs (lncRNAs) for risk stratification in cervical cancer (CC) and explored factors of prognosis, inflammatory microenvironment infiltrates, and chemotherapeutic therapies. Methods: The RNA-seq data and clinical information of CC were collected from the TCGA TARGET GTEx database and the TCGA database. lncRNAs and immune-related signatures were obtained from the GENCODE database and the ImPort database, respectively. We screened out immune-related lncRNA signatures through univariate Cox, LASSO, and multivariate Cox regression methods. We established an immune-related risk model of hub immune-related lncRNAs to evaluate whether the risk score was an independent prognostic predictor. The xCell and CIBERSORTx algorithms were employed to appraise the value of risk scores which are in competition with tumor-infiltrating immune cell abundances. The estimation of tumor immunotherapy response through the TIDE algorithm and prediction of innovative recommended medications on the target to immune-related risk model were also performed on the basis of the IC50 predictor. Results: We successfully established six immune-related lncRNAs (AC006126.4, EGFR-AS1, RP4-647J21.1, LINC00925, EMX2OS, and BZRAP1-AS1) to carry out prognostic prediction of CC. The immune-related risk model was constructed in which we observed that high-risk groups were strongly linked with poor survival outcomes. Risk scores varied with clinicopathological parameters and the tumor stage and were an independent hazard factor that affect prognosis of CC. The xCell algorithm revealed that hub immune-related signatures were relevant to immune cells, especially mast cells, DCs, megakaryocytes, memory B cells, NK cells, and Th1 cells. The CIBERSORTx algorithm revealed an inflammatory microenvironment where naive B cells (p < 0.01), activated dendritic cells (p < 0.05), activated mast cells (p < 0.0001), CD8+ T cells (p < 0.001), and regulatory T cells (p < 0.01) were significantly lower in the high-risk group, while macrophages M0 (p < 0.001), macrophages M2 (p < 0.05), resting mast cells (p < 0.0001), and neutrophils (p < 0.01) were highly conferred. The result of TIDE indicated that the number of immunotherapy responders in the low-risk group (124/137) increased significantly (p = 0.00000022) compared to the high-risk group (94/137), suggesting that the immunotherapy response of CC patients was completely negatively correlated with the risk scores. Last, we compared differential IC50 predictive values in high- and low-risk groups, and 12 compounds were identified as future treatments for CC patients. Conclusion: In this study, six immune-related lncRNAs were suggested to predict the outcome of CC, which is beneficial to the formulation of immunotherapy.

Renal cell carcinoma (RCC) is the third common solid tumor in the urinary system with a high distant metastasis rate. The five-year survival rate of RCC has reached 75%, benefiting from the emergence and update of multiple treatments, while its pathogenesis and prognostic markers are still unclear. In this study, we committed to explore a prognostic ceRNA network that could participate in the development of RCC and had not been studied yet. We screened nine immune-related hub genes (AGER, HAMP, LAT, LTB4R, NR3C2, SEMA3D, SEMA3G, SLC11A1, and VAV3) using data of The Cancer Genome Atlas Kidney Clear Cell Carcinoma database (TCGA-KIRC) through survival analysis and the cox proportional hazard model. Next, we successfully constructed a ceRNA network of two mRNA (NR3C2 and VAV3), miRNA (hsa-miR-186-5p), and lncRNA (NNT-AS1) for ccRCC based on numerous online bioinformatics tools and Cytoscape. Finally, we predicted five potential drugs (clemizole, pentolonium, dioxybenzone, Prestwick-691, and metoprolol) based on the above results.

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Almost 75% of renal cancers are renal clear cell carcinomas (KIRC). Accumulative evidence indicates that epigenetic dysregulations are closely related to the development of KIRC. Cancer immunotherapy is an effective treatment for cancers. The aim of this study was to identify immune-related differentially expressed genes (IR-DEGs) associated with aberrant methylations and construct a risk assessment model using these IR-DEGs to predict the prognosis of KIRC. Two IR-DEGs (SLC11A1 and TNFSF14) were identified by differential expression, correlation analysis, and Cox regression analysis, and risk assessment models were established. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.6907. In addition, we found that risk scores were significantly associated with 31 immune cells and factors. Our present study not only shows that two IR-DEGs can be used as prognosis signatures for KIRC, but also provides a strategy for the screening of suitable prognosis signatures associated with aberrant methylation in other cancers.