Serum albumin as a prognostic predictor reflecting host immunity in patients with non-small cell lung cancer

Objective:Serum albumin(ALB)can transport nutrients to circulating and local immune cells by passing through blood vessels and has attracted attention as a prognostic predictor of non-small cell lung cancer(NSCLC)because it reflects the host immunity from peripheral blood(PBL)to the tumor microenvironment. Methods:Clinical data regarding the PBL and tumor tissues were obtained at The First Hospital of Jilin University between February 2009 and March 2017.We detected indices of glucose and lipid metabolism,classified and counted PBL lymphocytes using flow cy-tometry,determined the tumor-infiltrating lymphocytes by quantitative immunofluorescence,and analyzed the T-cell receptor(TCR)rep-ertoire by high-throughput sequencing of the TCR β-chain.The correlations between ALB and metabolic immune indices were analyzed by t tests and Pearson chi-square test. Results:A total of 211 enrolled NSCLC patients were divided into a relatively high-ALB group(>41.75 g/L,n = 56)and a low-ALB group(≤41.75 g/L,n = 155);patients with high ALB had lower Treg cells(P<0.05)and more CD8+ cytotoxic T cells in the PBL(P<0.01)and a higher proportion of stromal CD8+ tumor-infiltrating lymphocytes(P = 0.047)than patients with low ALB.High ALB was also significantly related to more diversity in the TCR repertoire(P = 0.0021,r2 = 0.5481).Moreover,ALB was identified as an in-dependent prognostic factor based on a multivariate Cox regression analysis(P = 0.032;hazard ratio(HR)= 1.804;95%confidence interval(CI)= 1.035-3.146).The median overall survival in patients with low ALB vs high ALB was 28.2 vs 42.2 months(P=0.0142),respectively.Among patients with nonmetastatic NSCLC(stage Ⅰ-Ⅲ),there was a higher incidence of distant metastasis in the low-ALB group than that in the high-ALB group(41.3%and 22.2%,P=0.043).A low ALB also had a strong association with a higher risk for disease progression(P<0.001)and death(P<0.01;HR = 0.555;95%CI= 0.312-0.988). Conclusions:Albumin could affect the host immunity,and high ALB predicted a reduced risk of distant metastasis and improved the prognosis in NSCLC patients.

Human umbilical cord-derived mesenchymal stem cells promote repair of neonatal brain injury caused by hypoxia/ischemia in rats

Administration of human umbilical cord-derived mesenchymal stem cells(hUC-MSCs)is believed to be an effective method for treating neurodevelopmental disorde rs.In this study,we investigated the possibility of hUC-MSCs treatment of neonatal hypoxic/ischemic brain injury associated with maternal immune activation and the underlying mechanism.We established neonatal rat models of hypoxic/ischemic brain injury by exposing pregnant rats to lipopolysaccharide on day 16 or 17 of pregnancy.Rat offspring were intranasally administe red hUC-MSCs on postnatal day 14.We found that polypyrimidine tract-binding protein-1(PTBP-1)participated in the regulation of lipopolysaccharide-induced maternal immune activation,which led to neonatal hypoxic/ischemic brain injury.Intranasal delive ry of hUC-MSCs inhibited PTBP-1 expression,alleviated neonatal brain injury-related inflammation,and regulated the number and function of glial fibrillary acidic protein-positive astrocytes,there by promoting plastic regeneration of neurons and im p roving brain function.These findings suggest that hUC-MSCs can effectively promote the repair of neonatal hypoxic/ischemic brain injury related to maternal immune activation through inhibition of PTBP-1 expression and astrocyte activation.

A brand new era of cancer immunotherapy: breakthroughs and challenges

Immunotherapy has opened a new era in cancer treatment.Drugs represented by immune checkpoint inhibitors have led to important breakthroughs in the treatment of various solid tumors,greatly improving the survival rate of cancer patients.Many types of immunotherapeutic drugs have become widely available;however,their efficacy is variable,and relatively few patients with advanced cancer experience life-altering durable survival,reflecting the complex and highly regulated nature of the immune system.The research field of cancer immunotherapy(CIT)still faces many challenges in pursuing the broader social goal of“curing cancer.”Increasing attention has been paid to strengthening the understanding of the molecular or cellular drivers of resistance to immunotherapy,actively exploring more effective therapeutic targets,and developing combination therapy strategies.Here,we review the key challenges that have emerged in the era of CIT and the possible solutions or development directions to overcome these difficulties,providing relevant references for basic research and the development of modified clinical treatment regimens.

Cost-effectiveness of programmed cell death ligand 1 testing and tumor mutational burden testing of immune checkpoint inhibitors for advanced non-small cell lung cancer

To the Editor:Worldwide,lung cancer,particularly non-small cell lung cancer(NSCLC),is the leading cause of tumor-related death.Cost-effectiveness analysis show no economic benefits for advanced NSCLC patients over chemotherapy.[1]Furthermore,tests such as programmed cell death ligand 1(PD-L1)and tumor mutational burden(TMB)tests,evaluated via immunohistochemical methods and next-generation sequencing,respectively,are widely used for screening potential beneficiaries of immune checkpoint inhibitors(ICIs).However,these two methods have different predictive values,making their comprehensive evaluation the focus of the current controversy.