Prognostic Factors for Survival of Stage IB Upper Lobe Non-small Cell Lung Cancer Patients: A Retrospective Study in Shanghai, China

Objective: To identify clinical and pathologic factors that were associated with the survival of stage IB upper lobe non-small cell lung cancer (NSCLC) patients. Methods: A retrospective study of 147 subjects who had undergone curative resection for stage IB upper lobe NSCLC was performed. Patients who had received any adjuvant or neo-adjuvant chemotherapy were excluded. Survival function curves were estimated using the Kaplan-Meier procedure. Crude and adjusted hazard ratios (HRs) of potential prognostic factors were estimated using Cox proportional hazards models. Results: Five factors, including age, tumor size, histologic grade of differentiation, number of removed superior mediastinal lymph node stations and presence of visceral pleura invasion, were significantly and independently associated with mortality risk. Adjusted HRs were 2.6 [95% confidence interval (95% CI): 1.1?6.5] and 4.6 (95% CI: 1.9?11) for those aged 58?68 years and those >68 years, respectively, relative to those aged <58 years. HRs for those with poorly and moderately differentiated tumors were 6.4 (95% CI: 2.3?18) and 1.4 (95% CI: 0.7?2.8), respectively. HRs for those with tumor size 3.1?5 cm and >5 cm (vs ?3.0 cm) were 2.3 (95% CI: 1.1?4.9) and 4.3 (95% CI: 1.9?10), respectively. The presence of visceral pleura invasion also increased the risk of mortality (HR=4.0, 95% CI: 1.3?12). Conclusion: Advanced age, larger tumor size, poorly differentiated histology, smaller number of removed superior mediastinal lymph node stations, and presence of visceral pleura invasion were associated with poor survival of surgically treated stage IB upper lobe NSCLC patients.

IMpower210:A phase Ⅲ study of second-line atezolizumab vs. docetaxel in East Asian patients with non-small cell lung cancer

Objective: IMpower210(NCT02813785) explored the efficacy and safety of single-agent atezolizumab vs.docetaxel as second-line treatment for advanced non-small cell lung cancer(NSCLC) in East Asian patients.Methods: Key eligibility criteria for this phase Ⅲ, open-label, randomized study included age ≥18 years;histologically documented advanced NSCLC per the Union for International Cancer Control/American Joint Committee on Cancer staging system(7th edition);Eastern Cooperative Oncology Group performance status of 0 or 1;and disease progression following platinum-based chemotherapy for advanced or metastatic NSCLC. Patients were randomized 2:1 to receive either atezolizumab(1,200 mg) or docetaxel(75 mg/m^(2)). The primary study endpoint was overall survival(OS) in the intention-to-treat(ITT) population with wild-type epidermal growth factor receptor expression(ITT EGFR-WT) and in the overall ITT population.Results: Median OS in the ITT EGFR-WT population(n=467) was 12.3 [95% confidence interval(95% CI),10.3-13.8] months in the atezolizumab arm(n=312) and 9.9(95% CI, 7.8-13.9) months in the docetaxel arm[n=155;stratified hazard ratio(HR), 0.82;95% CI, 0.66-1.03]. Median OS in the overall ITT population was 12.5(95% CI, 10.8-13.8) months with atezolizumab treatment and 11.1(95% CI, 8.4-14.2) months(n=377) with docetaxel treatment(n=188;stratified HR, 0.87;95% CI, 0.71-1.08). Grade 3/4 treatment-related adverse events(TRAEs) occurred in 18.4% of patients in the atezolizumab arm and 50.0% of patients in the docetaxel arm.Conclusions: IMpower210 did not meet its primary efficacy endpoint of OS in the ITT EGFR-WT or overall ITT populations. Atezolizumab was comparatively more tolerable than docetaxel, with a lower incidence of grade3/4 TRAEs.

Acetylcholine receptor pathway in lung cancer: New twists to an old story

Genome-wide association studies revealed that allelic variation in the α5-α3-β4 nicotine acetylcholine receptor(n ACh R) cluster on chromosome 15q24-15q25.1 was associated with lung cancer risk. n ACh Rs are membrane ligand-gated cation channels whose activation is triggered by the binding of the endogenous neurotransmitter acetylcholine(ACh) or other biologic compounds including nicotine. n ACh Rs have been found on lung cancer cells, underscoring the idea that the non-neuronal n ACh R pathway has important implications for lung cancer. Several studies focusing on the treatment with n ACh R antagonists with improved selectivity might trigger novel strategies for the intervention and prevention of lung cancer. Here we review the genetic risk factors for lung cancer in the n ACh R gene cluster, the roles of nicotine receptors, and the molecular mechanisms of acetylcholine receptor pathways to lead to more opportunities for intervention and prevention of lung cancer.

Targeting FGFR in non-small cell lung cancer:implications from the landscape of clinically actionable aberrations of FGFR kinases

Objective:Dysfunction in fibroblast growth factor receptor(FGFR)signaling has been reported in diverse cancer types,including non-small cell lung cancer(NSCLC).The frequency of FGFR aberrations in Chinese NSCLC patients is therefore of great clinical significance.Methods:A total of 10,966 NSCLC patients whose tumor specimen and/or circulating cell-free DNA(cf DNA)underwent hybridization capture-based next-generation sequencing were reviewed.Patients'clinical characteristics and treatment histories were also evaluated.Results:FGFR aberrations,including mutations,fusions,and gene amplifications,were detected in 1.9%(210/10,966)of the population.FGFR abnormalities were more frequently observed in lung squamous cell carcinomas(6.8%,65/954)than lung adenocarcinomas(1.3%,128/9,596).FGFR oncogenic mutations were identified in 19 patients(~0.17%),of which,68%were male lung squamous cell carcinoma patients.Eleven out of the 19 patients(58%)had concurrent altered PI3 K signaling,thus highlighting a potential combination therapeutic strategy of dual-targeting FGFR and PI3 K signaling in such patients.Furthermore,FGFR fusions retaining the intact kinase domain were identified in 12 patients(0.11%),including 9 FGFR3-TACC3,1 FGFR2-INA,1 novel FGFR4-RAPGEFL1,and 1 novel fusion between the FGFR1 and SLC20 A25′-untranslated regions,which may have caused FGFR1 overexpressions.Concomitant EGFR mutations or amplifications were observed in 6 patients,and 4 patients received anti-EGFR inhibitors,in whom FGFR fusions may have mediated resistance to anti-EGFR therapies.FGFR amplification was detected in 24 patients,with the majority being FGFR1 amplifications.Importantly,FGFR oncogenic mutations,fusions,and gene amplifications were almost always mutually exclusive events.Conclusions:We report the prevalence of FGFR anomalies in a large NSCLC population,including mutations,gene amplifications,and novel FGFR fusions.

Antiangiogenic agents combined with chemotherapy in non-small cell lung cancer

As a targeted therapy, antiangiogenic treatment has been increasingly studied for advanced non-small cell lung cancer(NSCLC) and has proven effective for the treatment of advanced NSCLC. Bevacizumab, a monoclonal antibody targeting angiogenesis, is the only antiangiogenic agent approved for use in combination with first-line chemotherapy for non-squamous NSCLC. Small-molecule inhibitors targeting the tyrosine kinase receptor have also shown promise when combined with standard chemotherapeutic agents in patients with advanced NSCLC. However, unlike bevacizumab, not all other antiangiogenic agents show significant benefits when combined with chemotherapy. As for the failures of most other combinations, the combination schedule may be an important reason that has so far been overlooked in clinical trials. This article reviews the combination of angiogenic agents with chemotherapy in the treatment of NSCLC.

Perioperative chemotherapy of stage Ⅲ N2 non-small cell lung cancer

Patients with stage Ⅲ N2 non-small cell lung cancer （NSCLC） are more than one third of all NSCLC patients. The 5-year survival rate of them is approximately 15%. From therapeutic views, stage ⅢA N2 of 97 International Lung Cancer Staging System is an obvious hetero-combination, which includes mediastinal lymph node metastasis based on microscope after postoperative examination and N2 of single station or N2 of multiple stations based on computerized tomographic scanning and N2 of mediastinal lymph node mixed together. The different status of stage N2 lead to different prognosis. Andre et al reported the results of continuous surgery in 702 patients with NSCLC, which showed that N2 of single station based on microscope, 5-year survival rate was 34% （244 cases）, N2 of multiple stations based on microscope, 5-year survival rate was 11% （788 cases）, N2 of single station based on radiograph, 5-year survival rate was 8% （118 cases）,

MicroRNA (let-7b-5p)-targeted DARS2 regulates lung adenocarcinoma growth by PI3K/AKT signaling pathway

Background:The aberrant intraellular expression of a mitochondrial aspartyl tRNA synthetase 2(DARS2)has been reported in human cancers.Nevertheless its critical role and detailed mechanism in lung adenocarcinoma(LUAD)remain unexplored.Methods:Initially,The Cancer Genome Atlas(TCGA)based Gene Expression Profiling Interactive Analysis(GEPIA)database (http:/gepia.cancer-pku.cn/)was used to analyze the prognostic relevance of DARS2 expression in LUAD.Further,cell counting kit(CCK)8,immunostaining,and transwell invasion assays in LUAD cell lines in vitro,as well as DARS2 silence on LUAD by tumorigenicity experiments in wivo in nude mice,were performed.Besides,we analyzed the expression levels of p-PI3K(phosphorylated Phosphotylinosital3 kinase),PI3K,AKT(Protein Kinase B),p-AKT(phosphorylated Protein Kinase B),PCNA(proliferating cell nudear antigen),cleaved-caspase 3,E cadherin,and N-cadherin proteins using the Westem blot analysis.Results:LUAD tissues showed higher DARS2 expression compared to normal tissues.Upregulation of DARS2 could be related to Tumor-Node-Metastasis(TNM)stage,high lymph node metastasis,and inferior prognosis.DARS2 silence decreased the proliferation,migration,and invasion abilities of LUAD cells.In addition,the DARS2 downregulation decreased the PCNA and N-cadherin expression and increased cleaved:caspase 3 and E cadherin expressions in LUAD cells,coupled with the inactivation of the PI3K/AKT signaling pathway.Moreover,DARS2 silence impaired the tumonigenicity of LUAD in vivo.Interestingly,let:7b-5p could recognize DARS2 through a complementary sequence.Mechanistically,the increased let 7b 5p expression attenuated the promo oncogenic action of DARS2 during LUAD progression,which were inversely correlated to each other in the LUAD tssues Conclusion:In summary,let 7b-5p,downregulated DARS2 expression,regulating the progression of LUAD cells by the PI3K/AKT signaling pathway.

SHR-A1811(antibody-drug conjugate)in advanced HER2-mutant non-small cell lung cancer:a multicenter,open-label,phase 1/2 study

A dose-escalation and expansion,phase 1/2 study(ClinicalTrials.gov,NCT04818333)was conducted to assess the novel antibodydrug conjugate SHR-A1811 in pretreated HER2-altered advanced non-small cell lung cancer(NSCLC).Here,we report results from the phase 1 portion.Patients who had previously failed or were intolerant to platinum-based chemotherapy were enrolled and received SHR-A1811 intravenously at doses of 3.2 to 8.0 mg/kg every 3 weeks.Dose escalation followed a Bayesian logistic regression model that included overdose control,with subsequent selection of tolerable levels for dose expansion.Overall,63 patients were enrolled,including 43 receiving a recommended dose for expansion of 4.8 mg/kg.All patients had HER2-mutant disease.Dose-limiting toxicity occurred in one patient in the 8.0 mg/kg dose cohort.Grade≥3 treatment-related adverse events occurred in 29(46.0%)patients.One patient in the 6.4 mg/kg cohort died due to interstitial lung disease.As of April 11,2023,the 4.8 mg/kg cohort showed an objective response rate of 41.9%(95%Cl 27.0-57.9),and a disease control rate of 95.3%(95%Cl 84.2-99.4).The median duration of response was 13.7 months,with 13 of 18 responses ongoing.The median progression-free survival was 8.4 months(95%CI 7.1-15.0).SHR-A1811 demonstrated favourable safety and clinically meaningful efficacy in pretreated advanced HER2-mutantNSCLC.

Orient-31模式讨论:免疫治疗在驱动基因阳性的晚期NSCLC靶向耐药后的探索

靶向治疗的出现极大地提高了携带驱动基因突变的晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的生存率。对于表皮生长因子受体(epidermal growth factor receptor,EGFR)突变的肺癌患者,第三代EGFR酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)一线治疗的中位无进展生存期(progression-free survival,PFS)达到了18~21个月左右[1]。但对于EGFR-TKI治疗耐药后的NSCLC患者,仍缺乏有效的治疗方案。既往研究表明,EGFR-TKI耐药后的患者继续EGFR-TKI联合化疗未能提高生存获益[2]。

Trends and hotspots in gastrointestinal neoplasms risk assessment: A bibliometric analysis from 1984 to 2022

BACKGROUND Gastrointestinal neoplasm(GN)significantly impact the global cancer burden and mortality,necessitating early detection and treatment.Understanding the evolution and current state of research in this field is vital.AIM To conducts a comprehensive bibliometric analysis of publications from 1984 to 2022 to elucidate the trends and hotspots in the GN risk assessment research,focusing on key contributors,institutions,and thematic evolution.METHODS This study conducted a bibliometric analysis of data from the Web of Science Core Collection database using the"bibliometrix"R package,VOSviewer,and CiteSpace.The analysis focused on the distribution of publications,contributions by institutions and countries,and trends in keywords.The methods included data synthesis,network analysis,and visualization of international collaboration networks.RESULTS This analysis of 1371 articles on GN risk assessment revealed a notable evolution in terms of research focus and collaboration.It highlights the United States'critical role in advancing this field,with significant contributions from institutions such as Brigham and Women's Hospital and the National Cancer Institute.The last five years,substantial advancements have been made,representing nearly 45%of the examined literature.Publication rates have dramatically increased,from 20 articles in 2002 to 112 in 2022,reflecting intensified research efforts.This study underscores a growing trend toward interdisciplinary and international collaboration,with the Journal of Clinical Oncology standing out as a key publication outlet.This shift toward more comprehensive and collaborative research methods marks a significant step in addressing GN risks.CONCLUSION This study underscores advancements in GN risk assessment through genetic analyses and machine learning and reveals significant geographical disparities in research emphasis.This calls for enhanced global collaboration and integration of artificial intelligence to improve cancer prevention and treatment accuracy,ultimately enhancing worldwide patient care.

人源化免疫肺癌小鼠模型的建立及其在程序性死亡受体1抑制剂疗效评估中的作用

目的·建立表达程序性死亡配体1(programmed death-ligand 1,PD-L1)的人源化免疫肺癌动物模型,并研究该模型在评估程序性死亡受体1(programmed death-1,PD-1)抑制剂疗效中的作用。方法·取晚期非小细胞肺癌患者新鲜的活检组织样本,或恶性胸腔积液中的肿瘤细胞,接种至CB17-SCID小鼠(重症联合免疫缺陷小鼠)皮下,建立患者来源异种移植物模型(patient-derived xenograft model,PDX模型),通过免疫组织化学法检测PDX模型肿瘤PD-L1的表达情况。将成熟的人外周血单个核细胞与PDX模型肿瘤细胞混合后接种NCG小鼠(高度免疫缺陷小鼠),建立人源化免疫的肺癌PDX模型,并在该模型上验证PD-1抑制剂的疗效。结果·在16个临床来源样本建立的PDX模型中,有2个PD-L1表达为强阳性,4个表达为阳性,其余均为阴性。在PD-L1强阳性的人源化免疫肺癌PDX模型中,PD-1抑制剂信迪利单抗在初次给药后21 d的肿瘤生长抑制率为82.6%;在PD-L1阴性的人源化免疫肺癌PDX模型中,PD-1抑制剂未显示出抗肿瘤活性。结论·成功建立了表达PD-L1的人源化免疫肺癌小鼠模型,且能在该模型上评估PD-1抑制剂的疗效。

肺腺癌患者在Atezolizumab治疗过程中出现假性进展的案例报道

肺癌是全球癌症相关死亡的最常见原因。根据病理类型的不同,肺癌可分为非小细胞肺癌(non-small cell lung cancer, NSCLC)和小细胞肺癌(small cell lung cancer, SCLC)。其中NSCLC约占所有肺癌患者的85%。免疫检查点抑制剂(immune checkpoint inhibitors, ICIPs)是一类针对程序性死亡受体-1(programmed cell death protein 1, PD-1)及其配体(programmed death-ligand 1, PD-L1)的抑制剂,已有研究结果显示ICIPs在许多不同的癌症中具有良好且持久的抗癌疗效,其中抗PD-L1单克隆抗体Atezolizumab(MPDL3280)正在实体瘤和恶性血液病中开展临床研究。据报道,假性进展是免疫治疗中可能出现的独特现象之一。本文中我们报道了1例晚期NSCLC接受免疫治疗后发生假性进展的病例,希望这一案例可以更好地帮助临床医生恰当评估免疫治疗的疗效,并作出最恰当的治疗决策。

KEYNOTE-024的5年生存数据:帕博利珠单抗单药对比化疗一线治疗PD-L1 TPS≥50%转移性非小细胞肺癌

1 文献来源Reck M,Rodriguez-Abreu D,Robinson AG,et al.Five-year outcomes with pembrolizumab versus chemotherapy for metastatic non-small-cell lung cancer with PD-L1 tumor proportion score ≥50%[J].J Clin Oncol,2021,39(21):2339-2349.

ctDNA进行微小残留病灶监测和疾病复发预测

1文献来源Chen K,Zhao H,Shi Y,et al.Perioperative dynamic changes in circulating tumor DNA in patients with lung cancer(DYNAMIC)[J].Clin Cancer Res,2019,25(23):7058-7067.2证据水平1b。3背景既往研究表明,循环肿瘤DNA(circulating tumor DNA,ctDNA)水平反映了全身性肿瘤总负担。完全手术后,ctDNA水平应降低,并且随着肿瘤复发而升高。

ALK融合基因阳性非小细胞肺癌的临床研究进展

肺癌是世界上发病率最高的恶性肿瘤,且是癌症死亡的首要原因。80%~85%的肺癌为非小细胞肺癌(NSCLC),NSCLC中间变淋巴瘤激酶(ALK)融合基因阳性率为3%~7%。近年来,针对ALK融合基因的靶向治疗药物发展迅速,克唑替尼、艾乐替尼、劳拉替尼等ALK抑制剂的临床使用显著改善了ALK阳性晚期NSCLC患者的生存,而ALK融合基因阳性对早期NSCLC患者预后的影响尚不明确,其是否能从ALK抑制剂治疗中获益仍未可知。该文对ALK融合基因的作用机制、临床病理特征、检测方法、ALK融合基因阳性对NSCLC患者预后的影响及ALK抑制剂的最新进展进行简要阐述,以期为临床工作提供参考。

含空腔结构肺腺癌的CT特征与病理类型分析

目的:探究表现为含空腔结构肺腺癌的CT表现及病理类型分析。方法:共收集表现为含空腔结构肺腺癌52例,54枚,按CT特征分为如下几型。I型:肿瘤组织向腔外生长;II型:肿瘤组织向腔内生长,HI型:肿瘤组织环绕空腔生长;IV型:多房囊腔。分析病灶影像及病理类型特征。结果:含空腔结构肺腺癌病理亚型以乳头为主型最多(26枚,4&15%),HI型病灶最多见(27枚,50%),37枚病灶影响支气管。病灶具有分叶征(28枚,51.9%)、瘤肺界面清楚(46枚,85.2%)等传统肺腺癌的影像学恃征,各型病灶又具有各自特点。结论:含空腔结构肺腺癌病理类型以乳头样为主型,腔壁增厚或壁结节有助于诊断。

Effectiveness of PD-1/PD-L1 inhibitors in the treatment of lung cancer:Brightness and challenge

Immune checkpoint inhibitors(ICIs),especially inhibitors of the PD-1/PD-L1 axis,have significantly affected the outcomes of patients with lung cancer.Nivolumab and pembrolizumab have been approved as PD-1 blocking antibodies,whereas atezolizumab,avelumab,and durvalumab are approved as PD-L1 blocking antibodies by the United States Food and Drug Administration.However,which patient may benefit the most and how to identify patients at risk of primary or acquired resistance has not been completely defined.Meanwhile,close attention has been paid to the ongoing international and domestic clinical trials in Chinese patients with lung cancer.This review aimed to provide deep insight into the effectiveness of PD-1/PD-L1 inhibitors in patients with lung cancer,including the current settings for varied disease status,the predictive biomarkers,the resistance to ICIs,and the ongoing clinical trials in Chinese patients.

CircRNA在肺癌诊断与发生发展及耐药中的作用进展

肺癌在全球范围内的致死率一直居高不下。近年来针对多种分子分型的靶向药物已成为中晚期肺癌治疗的新有效手段,但是肺癌在早期诊断以及长期有效的治疗上仍然面临着严峻的挑战。环状RNA(circular RNA,circRNA)是一类具有环形结构的独特RNA分子,具有优异的稳定性以及表达特异性。越来越多的研究发现circRNA在肿瘤中表达异常,这种异常表达不仅与肿瘤的恶性相关,同时可以参与调控肿瘤进展,为肿瘤的诊断与治疗提供了新的思路。因此,本文就circRNA在肺癌中的表达、诊断、预后价值以及发生发展机制展开综述,以期为肺癌的早期诊断与治疗寻找新的靶点。

Xenograft tumors derived from malignant pleural effusion of the patients with non-small-cell lung cancer as models to explore drug resistance

Background:Non-small cell lung cancer(NSCLC)patients with epidermal growth factor receptor(EGFR)mutations or anaplastic lymphoma kinase(ALK)fusions show dramatic responses to specific tyrosine kinase inhibitors(TKIs);however,after 10-12 months,secondary mutations arise that confer resistance.We generated a murine xenograft model using patient-derived NSCLC cells isolated from the pleural fluid of two patients with NSCLC to investigate the mechanisms of resistance against the ALK-and EGFR-targeted TKIs crizotinib and osimertinib,respectively.Methods:Genotypes of patient biopsies and xenograft tumors were determined by whole exome sequencing(WES),and patients and xenograft-bearing mice received targeted treatment(crizotinib or osimertinib)accordingly.Xenograft mice were also treated for prolonged periods to identify whether the development of drug resistance and/or treatment responses were associated with tumor size.Finally,the pathology of patients biopsies and xenograft tumors were compared histologically.Results:The histological characteristics and chemotherapy responses of xenograft tumors were similar to the actual patients.WES showed that the genotypes of the xenograft and patient tumors were similar(an echinoderm microtu-bule-associated protein-like 4-ALK(EML4-ALK)gene fusion(patient/xenograft:CTC15035EML4-ALK)and EGFR L858R and T790M mutations(patient/xenograft:CTC15063EGFR L858R,T790M)).After continuous crizotinib or osimertinib treatment,WES data suggested that acquired ALK E1210K mutation conferred crizotinib resistance in the CTC15035EML4-ALK xenograft,while decreased frequencies of EGFR L858R and T790M mutations plus the appearance of v-RAF murine sarcoma viral oncogene homolog B(BRAF)G7V mutations and phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha(PIK3C2A)A86fs frame shift mutations led to osimertinib resistance in the CTC15063EGFR L858R,T790M xenografts.Conclusions:We successfully developed a new method of generating drug resistance xenograft models from liquid biopsies using microfluidic technology,which might be a useful tool to investigate the mechanisms of drug resist-ance in NSCLC.

Peripheral CD4^(+) T cell signatures in predicting the responses to anti-PD-1/PD-L1 monotherapy for Chinese advanced non-small cell lung cancer

Limited benefit population of immune checkpoint inhibitors makes it urgent to screen predictive biomarkers for stratifying the patients.Herein,we have investigated peripheral CD4^(+) T cell signatures in advanced non-small cell lung cancer(NSCLC)patients receiving anti-PD-1/PD-L1 treatments.It was found that the percentages of IFN-γand IL-17A secreting naïve CD4^(+) T cells(Tn),and memory CD4^(+) T cells(Tm)expressing PD-1,PD-L1 and CTLA-4 were significantly higher in responder(R)than non-responder(NonR)NSCLC patients associated with a longer progression free survival(PFS).Logistic regression analysis revealed that the baseline IFN-γ-producing CD4^(+) Tn cells and PD-1^(+)CD4^(+) Tm cells were the most significant signatures with the area under curve(AUC)value reaching 0.849.This was further validated in another anti-PD-1 monotherapy cohort.Conversely,high percentage of CTLA-4^(+)CD4^(+) Tm cells was associated with a shorter PFS in patients receiving anti-PD-L1 monotherapy.Our study therefore elucidates the significance of functional CD4^(+) Tn and Tm subpopulations before the treatment in predicting the responses to anti-PD-1 treatment in Chinese NSCLC patients.The fact that there display distinct CD4^(+) T cell signatures in the prediction to anti-PD-1 and anti-PD-L1 monotherapy from our study provides preliminary evidence on the feasibility of anti-PD-1 and anti-PD-L1 combination therapy for advanced NSCLC patients.