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| 1 | Challenges of evaluating immunotherapy efficacy in solid tumors显示文摘Immunotherapy is one of the most promising treatments for multiple tumor types.The significant clinical benefits and durable responses of immunotherapy have led to the emergence of various immune-related clinical response patterns that extend beyond those achieved with cytotoxic agents.Various studies investigated the efficacy of immunotherapy,including the effect on tumor size,long-term survival benefits,and the ability to overcome the particularly challenging survival curves tailing phenomenon.The current immune-related methods guidelines,such as immune-related Response Criteria(irRC),immune-related Response Evaluation Criteria in Solid Tumors(irRECIST),immune Response Evaluation Criteria in Solid Tumors(iRECIST),and immune-modified Response Evaluation Criteria in Solid Tumors(imRECIST),could be well-adapted to identify the heterogeneity of responses that appear in patients receiving immunotherapy,such as pseudoprogression(PsPD)and hyperprogressive disease(HPD),and to some extent to overcome the limitation of evaluating the efficacy of immunotherapy on tumor size by imaging.Additionally,a second type of evaluation method was proposed based on survival,which includes milestone analysis and restricted mean survival time.Currently,milestone analysis is a complementary tool to summarize and interpret trial results along with more conventional measures of survival and other less established metrics.A golden standard evaluation method to distinguish the efficacy of immunotherapy may improve the process of imaging and aid survival-based efficacy evaluation in patients with solid tumors. | Rilan Bai Wenqian Li Nawen Du Jiuwei Cui | 2019 | Chinese Journal of Cancer Research2019，31，6： | 8 |
| 2 | Focused evaluation of the roles of macrophages in chimeric antigen receptor (CAR) T cell therapy associated cytokine release syndrome显示文摘Cytokine release syndrome(CRS)is a major obstacle to the widespread clinical application of chimeric antigen receptor(CAR)T cell therapies.CRS can also be induced by infections(such as SARS-CoV-2),drugs(such as therapeutic antibodies),and some autoimmune diseases.Myeloid-derived macrophages play key roles in the pathogenesis of CRS,and participate in the production and release of the core CRS cytokines,including interleukin(IL)-1,IL-6,and interferon-γ.In this review,we summarize the roles of macrophages in CRS and discuss new developments in macrophage activation and the related mechanisms of cytokine regulation in CRS. | Hanfei Guo Lei Qian Jiuwei Cui | 2022 | Cancer Biology & Medicine2022，19，3： | 6 |
| 3 | Clinical challenges in neoadjuvant immunotherapy for non-small cell lung cancer显示文摘Immune checkpoint inhibitors(ICIs),a type of immunotherapy,have become one of the most important therapeutic options for first-and second-line treatment of advanced non-small cell lung cancer(NSCLC).Recent clinical studies have shown that immunotherapy can offer substantial survival benefits to patients with early-stage or resectable advanced NSCLC.However,considering the importance of timing when using ICIs and their associated adverse events(AEs),the advantages and disadvantages of using these agents need to be weighed carefully when deciding the use of a combined treatment.In addition,the inconsistency between imaging assessment and pathological results poses further challenges to the evaluation of efficacy of neoadjuvant immunotherapy.It is also important to develop new methodologies and discover suitable biomarkers that can be used to evaluate survival outcomes of immunotherapy and identify patients who would benefit the most from this treatment.In this review,we aimed to summarize previous results of ongoing clinical trials on neoadjuvant immunotherapy for lung cancer and discuss the challenges and future perspectives of this therapeutic approach in the treatment of resectable NSCLC. | Hanfei Guo Wenqian Li Lei Qian Jiuwei Cui | 2021 | Chinese Journal of Cancer Research2021，33，2： | 5 |
| 4 | Analysis of characteristics and predictive factors of immune checkpoint inhibitor-related adverse events显示文摘Objective:We aimed to retrospectively analyze the toxicity profiles and predictors of immune-related adverse events(irAEs)as well as the correlation between irAEs and the clinical efficacy of multi-type immune checkpoint inhibitors(ICIs)in patients with advanced pan-cancer in a real-world setting.Methods:We retrospectively analyzed data from 105 patients with advanced pan-cancer treated with multi-type ICIs at the First Hospital of Jilin University between January 1,2016 and August 1,2020.We used logistic regression analyses to investigate the associations of irAEs with clinical baseline characteristics,blood count parameters,and biochemical indicators during treatment.Receiver operating characteristic curves were used to determine cutoff values for parameters and area under the curve values.Kaplan–Meier and Cox multivariate regression analyses were performed to estimate the relationships of baseline characteristics and irAEs with progression-free survival(PFS)and overall survival(OS).Results:A lower relative lymphocyte count(cutoff=28.5%),higher albumin level(cutoff=39.05 g/L),and higher absolute eosinophil count(AEC)(cutoff=0.175×10^(9)/L)were significantly associated with the occurrence of irAEs,among which a higher AEC(cutoff=0.205×10^(9)/L)was strongly associated with skin-related irAEs[odds ratios(ORs)=0.163,P=0.004].Moreover,a higher lactate dehydrogenase level(cutoff=237.5 U/L)was an independent predictor of irAEs of grade≥3(OR=0.083,P=0.023).In immune cell subgroup analysis,a lower absolute count of CD8+CD28−suppressor T cells(OR=0.806;95%confidence interval:0.643–1.011;P=0.062),which are regulatory T lymphocytes,was associated with the occurrence of irAEs,although the difference was not statistically significant.Furthermore,a higher percentage of CD19+B cells was associated with the occurrence of irAEs of grade≥3(P=0.02)and grade≥2(P=0.051).In addition,patients with any grade of irAE had a significantly high PFS(8.37 vs.3.77 months,hazard ratios(HR)=2.02,P=0.0038)and OS(24.77 vs.13.83 months,HR=1.84;P=0.024).Conclusions:This retrospective study reports clinical profile data for irAEs in unselected patients in a real-world setting and explored some parameters that may be potential predictive markers of the occurrence,type,or grade of irAEs in clinical practice.Evidence of a correlation between safety and efficacy may facilitate a complete assessment of the risk-benefit ratio for patients treated with ICIs. | Rilan Bai Naifei Chen Xiao Chen Lingyu Li Wei Song Wei Li Yuguang Zhao Yongfei Zhang Fujun Han Zheng Lyu Jiuwei Cui | 2021 | Cancer Biology & Medicine2021，18，4： | 4 |
| 5 | Randomized,multicenter,open-label trial of autologous cytokine-induced killer cell immunotherapy plus chemotherapy for squamous non-small-cell lung cancer:NCT01631357显示文摘Dear Editor,Cytokine-induced killer(CIK)cells have been recognized as a new type of anti-tumor effector cells.CIK cells are a mixture of T lymphocytes.Among them,CD3+/CD56+T cells,which are rare in uncultured peripheral blood,are the main effector cells.CIK cells can proliferate rapidly in vitro,with stronger antitumor activity,broader target tumor spectrum,and lower adverse effect than other reported antitumor effector cells.1 Their ease of production in vitro and antitumor potential have made them suitable candidates for cell therapy regimens in solid and hematopoietic tumor treatments.1,2 Our previous retrospective study showed that the median progression-free survival(PFS)and overall survival(OS)in untreated,advanced non-small-cell lung cancer(NSCLC)patients who received CIK cell immunotherapy plus chemotherapy(13 and 24 months,respectively)were significantly longer than in those who received chemotherapy alone(6 and 10 months,respectively).2 But so far,there is no prospective,multicenter clinical study in lung cancer.Based on our previous study,we designed this randomized,multicenter,open-label trial to further evaluate the clinical efficacy of CIK cell immunotherapy plus chemotherapy in patients with advanced squamous NSCLC(ClinicalTrials.gov number,NCT01631357). | Liang Liu Quanli Gao Jingting Jiang Junping Zhang Xin Song Jiuwei Cui Yunbin Ye Zhiyu Wang Xinwei Zhang Xiubao Ren | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 2 |
| 6 | Antitumor effects of a purified polysaccharide from Rhodiola rosea and its action mechanism显示文摘 | Zibin Cai Wei Li Haotian Wang Weiqun Yan Yulai Zhou Guanjun Wang Jiuwei Cui Fang Wang | 2012 | Carbohydrate Polymers2012，，1： | 1 |
| 7 | The percentage of peripheral blood blasts on day 7 of induction chemotherapy predicts response to therapy and survival in patients with acute myeloid leukemia显示文摘 | Gao Sujun Tan Yehui Liu Xiaoliang Su Long Yu Ping Han Wei Cui Jiuwei Li Wei | 2014 | Chinese Medical Journal2014，，2： | 1 |
| 8 | Combination of radiofrequency ablation and sequential cellular immunotherapy improves progression‐free survival for patients with hepatocellular carcinoma显示文摘 | Jiuwei Cui Nanya Wang Hengjun Zhao Haofan Jin Guanjun Wang Chao Niu Hiroshi Terunuma Hua He Wei Li | 2014 | Int. J. Cancer2014，，： | 1 |
| 9 | Paclitaxel liposome for injection (Lipusu) plus cisplatin versus gemcitabine plus cisplatin in the first-line treatment of locally advanced or metastatic lung squamous cell carcinoma: A multicenter, randomized, open-label, parallel controlled clinical study显示文摘Background:Lipusu is the first commercialized liposomal formulation of pacli-taxel and has demonstrated promising efficacy against locally advanced lung squamous cell carcinoma(LSCC)in a small-scale study.Here,we conducted a multicenter,randomized,phase 3 study to compare the efficacy and safety of cis-platin plus Lipusu(LP)versus cisplatin plus gemcitabine(GP)as first-line treat-ment in locally advanced or metastatic LSCC.Methods:Patients enrolled were aged between 18 to 75 years,had locally advanced(clinical stage IIIB,ineligible for concurrent chemoradiation or surgery)or metastatic(Stage IV)LSCC,had no previous systemic chemother-apy and at least one measurable lesion as per the Response Evaluation Criteria in Solid Tumors(version 1.1)before administration of the trial drug.The primary endpoint was progression-free survival(PFS).The secondary endpoints included objective response rate(ORR),disease control rate(DCR),overall survival(OS),and safety profiles.To explore the possible predictive value of plasma cytokines for LP treatment,plasma samples were collected from the LP group at baseline and first efficacy evaluation time and were then subjected to analysis by 45-Plex ProcartaPlex Panel 1 to detect the presence of 45 cytokines using the Luminex xMAP technology.The correlation between treatment outcomes and dynamic changes in the levels of cytokines were evaluated in preliminary analyses.Results:The median duration of follow-up was 15.4 months.237 patients in the LP group and 253 patients in the GP group were included in the per protocol set(PPS).In the PPS,the median PFS was 5.2 months versus 5.5 months in the LP and GP group(hazard rtio[HR]:1.03,P=0.742)respectively.The median OS was 14.6 months versus 12.5 months in the LP and GP group(HR:0.83,P=0.215).The ORR(41.8%versus 45.9%,P=0.412)and DCR(90.3%versus 88.1%,P=0.443)were also similar between the LP and GP group.A significantly lower proportion of patients in the LP group experienced adverse events(AEs)leading to treatment interruptions(10.9%versus 26.4%,P<0.001)or treatment termination(14.3%versus 23.1%,P=0.011).The analysis of cytokine levels in the LP group showed that low baseline levels of 27 cytokines were associated with an increased ORR,and 15 cytokines were associated with improved PFS,with 14 cytokines,including TNF-a,IFN-y,IL-6,and IL-8,demonstrating an overlapping trend.Conclusion:The LP regimen demonstrated similar PFS,OS,ORR and DCR as the GP regimen for patients with locally advanced or metastatic LSCC but had more favorable toxicity profiles.The study also identified a spectrum of different cytokines that could be potentially associated with the clinical benefit in patients who received the LP regimen. | Jie Zhang Yueyin Pan Qin Shi Guojun Zhang Liyan Jiang Xiaorong Dong Kangsheng Gu Huijuan Wang Xiaochun Zhang Nong Yang Yuping Li Jianping Xiong Tienan Yi Min Peng Yong Song Yun Fan Jiuwei Cui Gongyan Chen Wei Tan Aimin Zang Qisen Guo Guangqiang Zhao Ziping Wang Jianxing He Wenxiu Yao Xiaohong Wu Kai Chen Xiaohua Hu Chunhong Hu Lu Yue Da Jiang Guangfa Wang Junfeng Liu Guohua Yu Junling Li Jianling Bai Wenmin Xie Weihong Zhao Lihong Wu Caicun Zhou | 2022 | Cancer Communications2022，42，1： | 1 |
| 10 | Multiplexed imaging of tumor immune microenvironmental markers in locally advanced or metastatic non-small-cell lung cancer characterizes the features of response to PD-1 blockade plus chemotherapy显示文摘Background:Although programmed cell death 1(PD-1)blockade plus chemotherapy can significantly prolong the progression-free survival(PFS)and overall survival(OS)in first-line settings in patients with driver-negative advanced non-small-cell lung cancer(NSCLC),the predictive biomarkers remain undetermined.Here,we investigated the predictive value of tumor immune microenvironmental marker expression to characterize the response features to PD-1 blockade plus chemotherapy.Methods:Tumor tissue samples at baseline were prospectively collected from 144 locally advanced or metastatic NSCLC patients without driver gene alterations who received camrelizumab plus chemotherapy or chemotherapy alone.Tumor immune microenvironmental markers,including PD-1 ligand(PDL1),CD8,CD68,CD4 and forkhead box P3,were assessed using multiplex immunofluorescence(mIF)assays.Kaplan-Meier curveswere used to determine treatment outcome differences according to their expression status.Mutational profiles were compared between tumors with distinct expression levels of these markers and their combinations.Results:Responders had significantly higher CD8/PD-L1(P=0.015)or CD68/PD-L1 co-expression levels(P=0.021)than non-responders in the camrelizumab plus chemotherapy group,while no difference was observed in the chemotherapy group.Patients with high CD8/PD-L1 or CD68/PD-L1 co-expression level was associated with significantly longer PFS(P=0.002,P=0.024;respectively)and OS(P=0.006,P=0.026;respectively)than those with low co-expression in camrelizumab plus chemotherapy group.When comparing survival in the camrelizumab plus chemotherapy with chemotherapy by CD8/PD-L1 co-expression stratification,significantly better PFS(P=0.003)and OS(P=0.032)were observed in high co-expression subgroups.The predictive value of CD8/PD-L1 and CD68/PD-L1 co-expression remained statistically significant for PFS and OS when adjusting clinicopathological features.Although the prevalence of TP53 or KRAS mutations was similar between patients with and without CD8/PD-L1 or CD68/PD-L1 co-expression,the positive groups had a significantly higher proportion of TP53/KRAS co-mutations than the negative groups(both 13.0%vs.0.0%,P=0.023).Notably,enriched PI3K(P=0.012)and cell cycle pathway(P=0.021)were found in the CD8/PD-L1 co-expression group.Conclusion:Tumor immune microenvironmental marker expression,especially CD8/PD-L1 or CD68/PD-L1 co-expression,was associated with the efficacy of PD-1 blockade plus chemotherapy as first-line treatment in patients with advanced NSCLC. | Fengying Wu Tao Jiang Gongyan Chen Yunchao Huang Jianying Zhou Lizhu Lin Jifeng Feng Zhehai Wang Yongqian Shu Jianhua Shi Yi Hu Qiming Wang Ying Cheng Jianhua Chen Xiaoyan Lin Yongsheng Wang Jianan Huang Jiuwei Cui Lejie Cao Yunpeng Liu Yiping Zhang Yueyin Pan Jun Zhao LiPing Wang Jianhua Chang Qun Chen Xiubao Ren Wei Zhang Yun Fan Zhiyong He Jian Fang Kangsheng Gu Xiaorong Dong Tao Zhang Wei Shi Jianjun Zou Xuejuan Bai Shengxiang Ren Caicun Zhou | 2022 | Cancer Communications2022，42，12： | 1 |
| 11 | Potential new applications of immunotherapy for neuroendocrine neoplasms:immune landscape,current status and future perspectives显示文摘Neuroendocrine neoplasms(NENs)are a highly heterogeneous class of tumors arising from neuroendocrine cells and peptidergic neurons.After failure of first-line treatment,patients have poor prognosis and limited treatment options.Immune checkpoint inhibitors(ICIs)may be a powerful means of increasing therapeutic efficacy for such patients,but ICIs alone have low response rates and short disease control durations in most NENs and may be effective for only a portion of the population.ICIs combined with other immunotherapies,targeted therapies,or cytotoxic drugs have achieved some efficacy in patients with NENs and are worthy of further exploration to assess their benefits to the population.In addition,accumulating experimental and clinical evidence supports that the interaction between neuroendocrine and immune systems is essential to maintain homeostasis,and assessment of this broad neuroendocrine-immune correlation is essential for NEN treatment.In this review,we summarize the immune microenvironment characteristics,advances in immunotherapy,predictive biomarkers of ICI efficacy for NENs,and the effects of common endocrine hormones on the immune system,highlighting possible new application areas for this promising treatment in neglected NENs. | Rilan Bai Wenqian Li Jiuwei Cui | 2022 | Cancer Biology & Medicine2022，19，12： | 0 |
| 12 | Reciprocal costimulatory molecules control the activation of mucosal type 3 innate lymphoid cells during engagement with B cells显示文摘Innate lymphoid cells(ILCs)are the counterpart of T helper cells in the innate immune system and share multiple phenotypes with T helper cells.Inducible T-cell costimulator(ICOS)is recognized on T cells and participates in T-cell activation and T and B-cell engagement in lymphoid tissues.However,the role of ICOS in ILC3s and ILC3-involved interactions with the immune microenvironment remains unclear.Here,we found that ICOS expression on human ILC3s was correlated with the activated state of ILC3s.ICOS costimulation enhanced the survival,proliferation,and capacity of ILC3s to produce cytokines(IL-22,IL-17A,IFN-γ,TNF,and GM-CSF).Via synergistic effects of ICOS and CD40 signaling,B cells promoted ILC3 functions,and ILC3-induced T-cellindependent B-cell IgA and IgM secretion primarily required CD40 signaling.Hence,ICOS is essential for the nonredundant role of ILC3s and their interaction with adjacent B cells. | Xinping Lv Shan Zhu Jing Wu Jinfeng Shi Qiuyu Wei Tete Li Ning Yang Chunyan Liu Lingli Qi Guoxia Zang Hang Cheng Zhiguang Yang Chengyan Jin Yusheng Wang Jiuwei Cui Hideki Ueno Yong-Jun Liu Jingtao Chen | 2023 | Cellular & Molecular Immunology2023，20，7： | 0 |
| 13 | Coexisting opportunities and challenges:In which scenarios can minimal/measurable residual disease play a role in advanced non-small cell lung cancer?显示文摘Curative therapy was not previously available for patients with advanced non-small cell lung cancer(NSCLC);thus,the concept of minimal/measurable(or molecular)residual disease(MRD)was not applicable to these patients.However,advances in targeted and immunotherapy have revolutionized the treatment landscape for patients with advanced NSCLC,with emerging evidence of long-term survival and even the hope of complete remission(CR)by imaging examination.The latest research shows that patients with oligometastatic lung cancer can benefit from local treatment.After removing the lesions,the choice of follow-up therapy and monitoring of the lesions could remain uncertain.MRD plays a role in identifying early-stage NSCLC patients with high risks of recurrence and determining adjuvant therapy after radical treatment.In recent years,evidence has been accumulating regarding the use of circulating cell-free tumor DNA(ctDNA)to assess MRD in solid tumors.This study discussed the possible applications of ctDNA-based MRD monitoring in advanced NSCLC and described the current challenges and unresolved problems in the application of MRD in advanced NSCLC. | Hanfei Guo Wenqian Li Bin Wang Neifei Chen Lei Qian Jiuwei Cui | 2021 | Chinese Journal of Cancer Research2021，33，5： | 0 |
| 14 | Advances in novel molecular typing and precise treatment strategies for small cell lung cancer显示文摘Small cell lung cancer(SCLC)is a high-grade neuroendocrine(NE)cancer characterized by high circulating tumor-cell burden and early extensive metastasis.Considering the complexity of SCLC genes and the immune microenvironment,their unique molecular heterogeneity profiles have been continuously explored.The understanding of SCLC subtypes has recently changed from traditional'classical'and'variant'types to'NE'and'non-NE'phenotypes and to the subtypes defined by major transcriptional regulators,which indicates the gradual revelation of high intratumoral heterogeneity and plasticity characteristics of SCLCs.Advances in genomics as well as the development of single-cell sequencing analysis and new preclinical models have helped investigators gain many new insights into SCLCs and the development of targeted therapy and immunotherapy strategies.This article provides an overview of changes in molecular typing,tumor heterogeneity,and plasticity and that of advances in the precise treatment of different subtypes of SCLC. | Rilan Bai Lingyu Li Xiao Chen Yuguang Zhao Wei Song Huimin Tian Jiuwei Cui | 2021 | Chinese Journal of Cancer Research2021，33，4： | 0 |
| 15 | Efficacy,safety and pharmacokinetics of Unecritinib(TQ-B3101)for patients with ROS1 positive advanced non-small cell lung cancer:a Phase I/II Trial显示文摘This phase I/II trial characterized the tolerability,safety,and antitumor activities of unecritinib,a novel derivative of crizotinib and a multi-tyrosine kinase inhibitor targeting ROS1,ALK,and c-MET,in advanced tumors and ROS1 inhibitor-naive advanced or metastatic non-small cell lung cancer(NSCLC)harboring ROS1 rearrangements.Eligible patients received unecritinib 100,200. | Shun Lu Hongming Pan Lin Wu Yu Yao Jianxing He Yan Wang Xiuwen Wang Yong Fang Zhen Zhou Xicheng Wang Xiuyu Cai Yan Yu Zhiyong Ma Xuhong Min Zhixiong Yang Lejie Cao Huaping Yang Yongqian Shu Wu Zhuang Shundong Cang Jian Fang Kai Li Zhuang Yu Jiuwei Cui Yang Zhang Man Li Xinxuan Wen Jie Zhang Weidong Li Jianhua Shi Xingxiang Xu Diansheng Zhong Tao Wang Jiajia Zhu | 2023 | Signal Transduction and Targeted Therapy2023，8，7： | 0 |
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