Anti-PD-1/PD-L1 immunotherapy reactivates T-cell activity to boost the antitumor effect and may trigger autoimmune toxicity in various organ systems involving eyeball and periocular structures at the same time. The rarity of ocular immune-related adverse events should not prevent us from paying attention to this issue because of the bad consequences of visual impairment. This is the first case report of anti-PD-1 sintilimab-induced bilateral optic neuropathy in a 76-year-old man with squamous non-small cell lung cancer (NSCLC). The patient presented with sudden vision blurring without pain in both eyes after three therapeutic cycles of sintilimab plus chemotherapy. Based on the ophthalmic examination, laboratory, and radiological results, our patient was diagnosed with optic neuropathy complication secondary to anti-PD-1 sintilimab treatment. Consequently, sintilimab was held and systemic steroids were administered. The follow-up review showed that the vision recovered and the size of the primary tumor continued to decrease with the response assessment as the partial response. In conclusion, this case report suggested that patients with NSCLC undergoing anti-PD-1/PD-L1 therapy should be closely monitored for ophthalmic assessment and alert to the occurrence of sintilimab-induced optic neuropathy.
Clear cell renal cell carcinoma (ccRCC), the most common type of RCC, typically produces no symptoms initially. Patients with ccRCC are at increased risk of developing advanced metastatic disease due to the absence of dependable and effective prognostic biomarkers. Therefore, it is particularly urgent to find optimal stratification of patients with ccRCC to distinguish the clinical benefits of different malignant degrees. Angiogenesis has a profound impact on the malignant behavior of renal cancer cells, and anti-angiogenic drugs have been applied to metastatic renal cancer patients. Moreover, immune function dysregulation is also a significant factor in tumorigenesis. We aim to construct a predictive model that combines angiogenesis and immune-related genes (AIRGs) to aid clinicians in predicting ccRCC prognosis.
The formation of human collagen requires the presence of Prolyl 3-hydroxylase 1 (P3H1), but the regulatory mechanism of P3H1 remained insufficiently understood. Our study aimed to identify the role of P3H1 in clear cell renal cell carcinoma (ccRCC). P3H1 expression in ccRCC was validated using multiple databases and in vitro experiments. We performed a correlation analysis of P3H1 with drug sensitivity, immune checkpoints, and immune cell infiltration using transcriptome and single-cell sequencing. Drawing upon the Encyclopedia of RNA Interactomes database, we selected P3H1 as the focal point of our investigation, meticulously uncovering the intricate network of microRNAs and lncRNAs that potentially orchestrate ceRNA mechanisms. This study employs a multidimensional approach integrating vitro assays and multi-omics bioinformatics analyses to investigate P3H1's impact on ccRCC prognosis, immune modulation, immune checkpoints, ceRNA regulatory network, drug sensitivity, and therapeutic responses, aiming to uncover new insights into its therapeutic potential and inform future clinical strategies.
Our preclinical work suggests that low-dose angiogenesis inhibition could potentiate programmed cell death protein 1 and programmed death-ligand 1 (PD-L1) blockade. In a cohort of our multicenter phase 1b and 2 study (NCT03083041), promising antitumor activity was observed with camrelizumab plus low-dose apatinib in chemotherapy-pretreated patients with advanced nonsquamous NSCLC. We hereby reported the results in treatment-naive patients (cohort 4) from the same study. Eligible patients had untreated advanced nonsquamous NSCLC with a high tumor mutational burden (TMB) (tissue TMB >10 mutations per megabase or blood TMB ≥1.54 mutations per megabase) and without sensitizing EGFR or ALK alterations. Patients received camrelizumab 200 mg intravenously every 2 weeks plus apatinib 250 mg orally once daily. The primary end point was the objective response rate (ORR) per investigator. A total of 25 patients were enrolled and treated. A total of 10 (40.0%) confirmed partial responses and 13 (52.0%) stable diseases were observed. The ORR was 40.0% (95% confidence interval [CI]: 21.1-61.3) and disease control rate was 92.0% (95% CI: 74.0-99.0). With a median follow-up of 19.5 months, the median progression-free survival was 9.6 months (95% CI: 5.5-not reached), whereas the overall survival was not reached; the median duration of response was 15.6 months (95% CI: 3.8-not reached). Similar ORR and progression-free survival were observed regardless of PD-L1 tumor proportion score (≥1% versus <1%). The most common treatment-related grade 3 or higher adverse events were increased gamma-glutamyltransferase (24.0%), increased alanine aminotransferase (16.0%), and abnormal hepatic function (16.0%). Frontline camrelizumab plus low-dose apatinib exhibited promising clinical activity with acceptable safety in patients with advanced nonsquamous NSCLC regardless of PD-L1 expression.
Abstract The m6A modification is a methylation of the adenosine N6 position, is a kind of reversible post-transcriptional modification of RNA. Moreover, this process has been shown to be associated with multiple tumor progression. Prostate cancer is the second most common cancer in men after lung cancer, and is closely related to m6A. However, previous studies were often limited to a few m6A related genes, and failed to fully understand the relationship between prostate cancer and m6A.Therefore, we used the CIBERSORT and ESTIMATE algorithms to define three m6A clusters based on the expression of m6A-related genes in 1099 PC patients. Subsequently, we identified three different m6A gene clusters based on the overlap of differentially expressed genes (DEGs) within the m6A clusters. In addition, by principal component analysis (PCA) was performed to calculate the m6A scores. The results showed that patients with high m6A scores had longer survival time and those with low scores had shorter survival time. Furthermore, the m6A score was negatively correlated with the tumor mutation burden (TMB) value of PC. Patients with higher m6A scores showed clinical benefit and advantage of immunotherapy, indicating that the m6A score is an accurate and valid predictor to assess the effect of immunotherapy. Overall, our study presents a new method for reference that can provide guidance for current immunotherapy and predict patient prognosis to help physicians make judgments about patient disease and treatment modalities, and can guide current research on immunotherapy strategies for PC.
Abstract Long non-coding RNA (lncRNA) plays an important role in tumor progression. Numerous studies show that lncRNA is strongly associated with prostate cancer progression. Our study confirmed that lncRNA HCG18 was highly expressed in prostate cancer (PC) and correlated with tumor progression in databases and cell lines. Western blot, RNA Pull-down, dual luciferase assay and rescue assays verified the correlation among lncRNA HCG18, miR-512-3p and hexokinase-2(HK-2). In general, the results showed that lncRNA HCG18 accelerated cell proliferation, migration, and invasion of PC via up-regulating HK-2 through sponging miR-512-3p, which provided a new direction for the diagnosis and treatment of PC.
Abstract Background Enolase is an essential enzyme in the process of glycolysis and has been implicated in cancer progression. Though dysregulation of ENOs has been reported in multiple cancers, their prognostic value and specific role in bladder cancer (BLCA) remain unclear. Methods Multiple databases were employed to examine the expression of ENOs in BLCA. The expression of ENO1 was also validated in BLCA cell lines and tissue samples by western blotting and immunohistochemistry. Kaplan–Meier analysis, ROC curve, univariate and multivariate Cox regression were performed to evaluate the predictive capability of the ENO1. Gene ontology (GO) and Gene Set Enrichment Analyses (GSEA) analysis were employed to perform the biological processes enrichment. Function experiments were performed to explore the biological role of ENO1 in BLCA. The correlation of ENO1 with immune cell infiltration was explored by CIBERSORT. Results By analyzing three ENO isoforms in multiple databases, we identified that ENO1 was the only significantly upregulated gene in BLCA. High expression level of ENO1 was further confirmed in BLCA tissue samples. Aberrant ENO1 overexpression was associated with clinicopathological characteristics and unfavorable prognosis. Functional studies demonstrated that ENO1 depletion inhibited cancer cell aggressiveness. Furthermore, the expression level of ENO1 was correlated with the infiltration levels of immune cells and immune-related functions. Conclusions Taken together, our results indicated that ENO1 might serve as a promising prognostic biomarker for prognosticating prognosis associated with the tumor immune microenvironment, suggesting that ENO1 could be a potential immune-related target against BLCA.
The hallmark of IgA nephropathy (IgAN) is the mesangial deposits of polymeric IgA. However, the source of IgA1 and the mechanism of deposition of IgA1 in the mesangium remain unknown. To better understand its pathogenesis, we investigated the expression of CD19(+)CD5(+)B cells and IgA1-positive cells in the tonsils of IgAN patients. Immunofluorescence was used to visualize the locations of CD19(+)CD5(+)B cells and IgA1-positive cells in the tonsils. In this study, it was demonstrated that CD19(+)CD5(+)B cells are usually found in germinal centers and in the capsule covering the upper parts of the nodules of lymphoid tissue (cap of the nodule). The expression of IgA1-positive cells in tonsil tissue can be seen in the cap of the nodule and subepithelial tissue. There is a significant relationship between IgA1 and CD19(+)CD5(+)B cells. The level of CD19(+)CD5(+)B cells is positively correlated to the severity of renal pathological changes. These findings suggest that CD19(+)CD5(+)B cells in the tonsils could have an impact on the pathogenesis of IgAN.
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