嵌合抗原受体T细胞免疫疗法治疗儿童恶性肿瘤的研究进展

嵌合抗原受体T细胞免疫疗法(CAR-T细胞疗法)是一种肿瘤免疫治疗方法,通过诱导T细胞的活化特异性识别肿瘤的靶点,释放细胞因子,发挥T细胞对肿瘤细胞的杀伤作用,可在共刺激因子协助下发挥持续的抗肿瘤作用。白血病、淋巴瘤等血液系统恶性肿瘤和神经母细胞瘤好发于儿童,具有较高的致死率,目前对于难治性和复发性肿瘤仍缺乏有效的治疗手段。随着CAR-T细胞疗法的研究深入,人们发现该法对上述儿童好发恶性肿瘤的治疗可发挥重要作用,对其难治性和复发性的病例也具有较好的疗效。本文将对CAR-T细胞疗法治疗儿童好发恶性肿瘤的相关研究进展进行综述。

The key elements analysis of Guangdong & Shenzhen ETS & tips for China national ETS construction

The only joint effort area of provincial and municipal governments resides in Guangdong Province and Shenzhen City in China's carbon emission trading system(ETS) pilots,which characterize the national carbon ETS plots.The present study on the operating experience from this area has important reference value for the national carbon ETS.Analysis and comparison of the key elements show many differences in coverage,total allowance,allowance allocation,and MRV mechanism between Guangdong and Shenzhen carbon ETS.The present study provides the following explanation:(1)the design characteristics of carbon ETS(e.g.coverage,total quotas,the allocation,and MRV mechanism) depend on the local geographical conditions and policy goals.The differences of economic structure in Guangdong Province and Shenzhen City result in different coverage,which then result in differences in other management elements.(2)The operating state of the carbon market is affected by overall design of carbon ETS:in the case of tighter total allowance,lower proportion of China Certified Emission Reductions,and harsher punishment,the carbon market is relatively active,which intends to produce carbon financial market.Based on deep analysis of operation characteristics of carbon ETS in Guangdong and Shenzhen,the present study suggests that(1)the allowance should be allocated freely at the beginning stage and then gradually transited to the voluntary paid auction;(2)the allowances assigned to companies shall be linked up with their energy-saving objectives;(3)the output fluctuations and economic influence on the allowance allocation should be properly handled to maintain the fairness and consistence of allowance allocation standards;(4)stable public expectation is one of the key elements to maintain the regular operation of carbon ETS;(5)constrained carbon emission behavior outside ETS can contribute to social justice;and(6)the improvement of professional skills of relevant personnel in the enterprise and independent third party can enhance carbon emissions data reliability.

Single-cell analysis reveals the potential mechanisms of pyrotinib resistance in non-small cell lung cancer

Dear Editor,Lung cancer still remains the leading cause of cancer death worldwide,80-90%of which are non-small cell lung cancer(NSCLC).In 2-3%of NSCLC patients,mutations in human epidermal growth factor receptor 2(HER2)have been identified as oncogenic drivers.However,HER2 has been poorly reported as a therapeutic target for advanced NSCLC despite of the outstanding improvements in breast cancer receiving HER2-targeting regimens.

An individualized immune signature of pretreatment biopsies predicts pathological complete response to neoadjuvant chemoradiotherapy and outcomes in patients with esophageal squamous cell carcinoma

No clinically available biomarkers can predict pathological complete response(pCR)for esophageal squamous cell carcinomas(ESCCs)with neoadjuvant chemoradiotherapy(nCRT).Considering that antitumor immunity status is an important determinant for nCRT,we performed an integrative analysis of immune-related gene profiles from pretreatment biopsies and constructed the first individualized immune signature for pCR and outcome prediction of ESCCs through a multicenter analysis.During the discovery phase,14 differentially expressed immune-related genes(DEIGs)with greater than a twofold change between pCRs and less than pCRs(<pCRs)were revealed from 28 pretreatment tumors in a Guangzhou cohort using microarray data.Ten DEIGs were verified by qPCR from 30 cases in a Beijing discovery cohort.Then,a four-gene-based immune signature(SERPINE1,MMP12,PLAUR,and EPS8)was built based on the verified DEIGs from 71 cases in a Beijing training cohort,and achieved a high accuracy with an area under the receiver operating characteristic curve(AUC)of 0.970.The signature was further validated in an internal validation cohort and an integrated external cohort(Zhengzhou and Anyang cohorts)with AUCs of 0.890 and 0.859,respectively.Importantly,a multivariate analysis showed that the signature was the only independent predictor for pCR.In addition,patients with high predictive scores showed significantly longer overall and relapse-free survival across multiple centers(P<0.05).This is the first,validated,and clinically applicable individualized immune signature of pCR and outcome prediction for ESCCs with nCRT.Further prospective validation may facilitate the combination of nCRT and immunotherapy.

The combination of novel immune checkpoints HHLA2 and ICOSLG:A new system to predict survival and immune features in esophageal squamous cell carcinoma

Studies on immune checkpoint inhibitors targeting B7-CD28 family pathways in esophageal squamous cell carcinoma(ESCC)have shown promising results.However,a comprehensive understanding of B7-CD28 family members in ESCC is still limited.This study aimed to construct a novel B7-CD28 family-based prognosis system to predict survival in patients with ESCC.We collected 179 cases from our previously published microarray data and 86 cases with qPCR data.Specifically,119 microarray data(GSE53624)were used as a training set,whereas the remaining 60 microarray data(GSE53622),all 179 microarray data(GSE53625)and an independent cohort with 86 qPCR data were used for validation.The underlying mechanism and immune landscape of the system were also explored using bioinformatics and immunofluorescence.We examined 13 well-defined B7-CD28 family members and identified 2 genes(ICSOLG and HHLA2)with the greatest prognostic value.A system based on the combination HHLA2 and ICOSLG(B7-CD28 signature)was constructed to distinguish patients as high-or low-risk of an unfavorable outcome,which was further confirmed as an independent prognostic factor.As expected,the signature was well validated in the entire cohort and in the independent cohort,as well as in different clinical subgroups.The signature was found to be closely related to immune-specific biological processes and pathways.Additionally,high-risk group samples demonstrated high infiltration of Tregs and fibroblasts and distinctive immune checkpoint panels.Collectively,we built the first,practical B7-CD28 signature for ESCC that could independently identify high-risk patients.Such information may help inform immunotherapy-based treatment decisions for patients with ESCC.

Nivolumab plus ipilimumab:a potential regimen to rewrite treatment guidelines for ESCC

The recent research published in The New England Journal of Medicine by Y.Doki et al.has reported the interim findings from the CheckMate 648,which is an international,multi-center,openlabel,and randomized phase 3 clinical trial to explore the role of dual immune checkpoints inhibitors combination for patients with advanced esophageal squamous cell carcinoma(ESCC)1.