A patient’s response to immune checkpoint inhibitors (ICIs) is a complex quantitative trait, and determined by multiple intrinsic and extrinsic factors. Three currently FDA-approved predictive biomarkers (progra1mmed cell death ligand-1 (PD-L1); microsatellite instability (MSI); tumor mutational burden (TMB)) are routinely used for patient selection for ICI response in clinical practice. Although clinical utility of these biomarkers has been demonstrated in ample clinical trials, many variables involved in using these biomarkers have poised serious challenges in daily practice. Furthermore, the predicted responders by these three biomarkers only have a small percentage of overlap, suggesting that each biomarker captures different contributing factors to ICI response. Optimized use of currently FDA-approved biomarkers and development of a new generation of predictive biomarkers are urgently needed. In this review, we will first discuss three widely used FDA-approved predictive biomarkers and their optimal use. Secondly, we will review four novel gene signature biomarkers: T-cell inflamed gene expression profile (GEP), T-cell dysfunction and exclusion gene signature (TIDE), melanocytic plasticity signature (MPS) and B-cell focused gene signature. The GEP and TIDE have shown better predictive performance than PD-L1, and PD-L1 or TMB, respectively. The MPS is superior to PD-L1, TMB, and TIDE. The B-cell focused gene signature represents a previously unexplored predictive biomarker to ICI response. Thirdly, we will highlight two combined predictive biomarkers: TMB+GEP and MPS+TIDE. These integrated biomarkers showed improved predictive outcomes compared to a single predictor. Finally, we will present a potential nucleic acid biomarker signature, allowing DNA and RNA biomarkers to be analyzed in one assay. This comprehensive signature could represent a future direction of developing robust predictive biomarkers, particularly for the cold tumors, for ICI response.

High sensitivity C-reactive protein (hsCRP) has been evaluated as a biomarker in stroke and relevant pathological diseases. While its predictive values in several pathological phenotypes have been confirmed, controversy exists among different studies. This review summarizes reports of the predictive values of hsCRP for the diagnosis, etiology, prognosis and mortality of stroke diseases. The current literature suggests that CRP expression is influenced by multiple factors, such as polymorphisms, the genomic backgrounds and gender. However, few reported studies analyzed data based on all these multiple factors. Future studies should focus on comprehensive analysis based on multiple factors.

Purpose To compare the efficacy and safety of conbercept and ranibizumab when administered according to a treat-and-extend (TREX) protocol for the treatment of neovascular age-related macular degeneration (AMD) in China. Patients and methods Between May 2014 and May 2015, 180 patients were treated in a 1 : 1 ratio using conbercept or ranibizumab from four hospitals. Patients received either conbercept 0.5 mg or ranibizumab 0.5 mg intravitreal injections. Follow-up time was 1 year and treated based on a TREX approach. Main outcomes and measures include best-corrected visual acuity (BCVA), using Early Treatment Diabetic Retinopathy Study (ETDRS); number of injections; central retinal thickness (CRT); and leakage of choroidal neovascularization before and after the treatment was analyzed by fluorescein fundus angiography and indocyanine green angiography. Results The 1-year visit was completed by 168 (93.3%) of patients. Mean BCVA was equivalent between two cohorts, and were improved by 12.7±7.770 and 12.3±7.269 letters in the conbercept and ranibizumab cohorts, respectively (P=0.624). There was no significant difference in measured CRT, with a mean decrease of 191.5 μm for conbercept and 187.8 μm for ranibizumab (P=0.773). There was a statistically significant difference (P=0.001) between the drugs regarding the number of treatments: 7.4 for conbercept and 8.7 for ranibizumab. The difference in the distribution of injection intervals was statistically significant between two groups (P=0.011). During the study, there were no cases of endophthalmitis or intraocular inflammation. Conclusion Both drugs had equivalent effects in visual and anatomic gains at 1 year when administered. In the conbercept group, longer treatment intervals were achieved with more patients.