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| 1 | Global land-surface air temperature change based on the new CMA GLSAT data set显示文摘The China Meteorological Administration(CMA)has recently developed a new global monthly homogenized land-surface air temperature data set.Based on this data set,we reanalyzed the change in global annual mean land-surface air temperature(LSAT)during three time periods(1901–2014,1979–2014 and 1998–2014).The results show that the linear trends of global annual mean LSAT were 0.104°C/decade,0.247°C/decade and 0.098°C/decade for the three periods,respectively.The trends were statistically significant except for the period 1998–2014,the period that | Xiubao Sun Guoyu Ren Wenhui Xu Qingxiang Li Yuyu Ren | 2017 | Science Bulletin2017，62，4： | 10 |
| 2 | Immunosuppressive checkpoint Siglec-15:a vital new piece of the cancer immunotherapy jigsaw puzzle显示文摘On March 5th, a novel immunosuppressive molecule,Siglec-15, was reported in Nature Medicine by Professor Lieping Chen1. Siglec-15 was reported in a wide variety of tumors. The molecule is not a simple replica of PD-1/PD-L1.Rather, the expressions of Siglec-15 and PD-L1 are mutually exclusive1, suggesting that Siglec-15 antibodies may be effective on tumors that are not responsive to anti-PD-1/PDL1 therapy. Siglec-15 potentially serves as a complementary therapeutic target and offers alternative treatments for many anti-PD-l/PD-Ll therapy unresponsive patients. This discovery generated a huge response. | Xiubao Ren | 2019 | Cancer Biology & Medicine2019，16，2： | 8 |
| 3 | Comprehensive insights into the effects and regulatory mechanisms of immune cells expressing programmed death-1/programmed death ligand 1 in solid tumors显示文摘The programmed cell death-1(PD-1)/programmed cell death ligand 1(PD-L1)signaling pathway is an important mechanism in tumor immune escape,and expression of PD-L1 on tumor cells has been reported more frequently.However,accumulating evidence suggests that PD-1/PD-L1 is also widely expressed on immune cells,and that regulation is also critical for tumor immune responses.In this review,we emphasized that under solid tumor conditions,the immunoregulatory effects of immune cells expressing PD-1 or PD-L1,affected the prognoses of cancer patients.Therefore,a better understanding of the mechanisms that regulate PD-1 or PD-L1 expression on immune cells would provide clear insights into the increased efficacy of anti-PD antibodies and the development of novel tumor immunotherapy strategies. | Min Liu Qian Sun Feng Wei Xiubao Ren | 2020 | Cancer Biology & Medicine2020，17，3： | 6 |
| 4 | A randomized phase II study of autologous cytokine-induced killer cells in treatment of hepatocelluar carcinoma显示文摘 | Xiaozhou Yu Hua Zhao Liang Liu Shui Cao Baozhu Ren Naining Zhang Xiumei An Jinpu Yu Hui Li Xiubao Ren | 2014 | Journal of Clinical Immunology2014，，2： | 5 |
| 5 | Memory stem T cells generated by Wnt signaling from blood of human renal clear cell carcinoma patients显示文摘Objective: Memory stem T cells(Tscm) have attracted attention because of their enhanced self-renewal, multipotent capacity, and anti-tumor capacities. However, little is known about Tscm in patients with renal clear cell carcinoma(RCC) and the role of Wnt signaling in these cells. We evaluated Tscm from RCC patients concerning their activation of Wnt signaling in vitro and explored the mechanism of preferential survival.Methods: Flow cytometry identified surface markers and cytokines produced from accumulated Tscm in the presence of the glycogen synthase kinase beta inhibitor TWS119. Apoptosis was evaluated after induction using tumor necrosis factor-alpha.Immunofluorescence and Western blot analyses were used to investigate the activation of the nuclear factor-kappa B(NF-КB)pathway.Results: RCC patients had a similar percentage of CD4^+ and CD8^+ Tscm as healthy donors. Activation of Wnt signaling by TWS119 resulted in the accumulation of Tscm in activated T cells, but reversal of differentiated T cells to Tscm was not achieved.Preferential survival of Tscm was associated with increased anti-apoptotic ability mediated downstream of the NF-КB activation pathway.Conclusions: The finding that Tscm can accumulate by Wnt signaling in vitro in blood from RCC patients will help in devising new cancer therapy strategies of Tscm-based adoptive immunotherapy, such as dendritic cell-stimulated Tscm, and T cell receptor or chimeric antigen receptor-engineered Tscm. | Cihui Yan Jingjing Chang Xinmiao Song Fan Yan Wenwen Yu Yang An Feng Wei Lili Yang Xiubao Ren | 2019 | Cancer Biology & Medicine2019，16，1： | 4 |
| 6 | Ferritin as a diagnostic, differential diagnostic, and prognostic marker for immune-related adverse events显示文摘Objective:Distinguishing immune-related adverse events(irAEs)caused by immune checkpoint inhibitors(ICIs)from the AEs caused by chemotherapy,targeted therapy,or infection is highly difficult.This study offers new insights into evaluating the diagnosis,differential diagnostic,and prognostic value of ferritin for irAEs induced by ICIs.Methods:From December 1,2018,to April 1,2019,we examined 318 patients with malignant tumors who received serum ferritin monitoring.The cohort comprised 231 patients treated with PD-1 inhibitor or combination with chemotherapy,and 87 patients treated with chemotherapy.Of the 231 patients,90 had irAEs(irAE group),70 had non-irAEs(non-irAE group),67 had no AEs(no irAE-non irAE group),and 4 had unclassified AEs.In the 87 patients,60 had AEs(AE group),and 27 had no AEs(no AE group).Statistical analyses were conducted with nonparametric Mann-Whitney tests.Results:At the onset of AEs in the irAE group,ferritin(normal range,35–150μg/L)rose to a median of 927μg/L(range,117–17,825μg/L)from 86μg/L at baseline(range,29–421μg/L)(P<0.001).Ferritin levels at the onset of AEs in the irAE group were significantly higher than those in the non-irAE group(median,81μg/L;range,32–478μg/L)(P<0.001)and the AE group(median,103μg/L;range,23–712μg/L)(P<0.001).After treatment in the irAE group,ferritin continuously decreased to a normal range in recovered patients,showed no significant changes in stable patients,and continued to rise in patients who died.Conclusions:Ferritin can be used as a diagnostic,differential diagnostic,and prognostic marker for irAEs in patients treated with ICIs. | Weihong Zhang Yuan Meng Lin Yang Meng Shen Li Zhou Runmei Li Yang Wang Weijiao Du Yanjuan Xiong Ying Han Xinwei Zhang Liang Liu Xiubao Ren | 2021 | Cancer Biology & Medicine2021，18，4： | 4 |
| 7 | Exhausted T cells and epigenetic status显示文摘Exhausted T cells are a group of dysfunctional T cells,which are present in chronic infections or tumors.The most significant characteristics of exhausted T cells are attenuated effector cytotoxicity,reduced cytokine production,and upregulation of multiple inhibitory molecular receptors(e.g.,PD-1,TIM-3,and LAG-3).The intracellular metabolic changes,altered expression of transcription factors,and a unique epigenetic landscape constitute the exhaustion program.Recently,researchers have made progress in understanding exhausted T cells,with the definition and identification of exhausted T cells changing from phenotypebased to being classified at the transcriptional and epigenetic levels.Recent studies have revealed that exhausted T cells can be separated into two subgroups,namely TCF1^(+)PD-1^(+)progenitor-like precursor exhausted cells and TCF1-PD-1^(+)terminally differentiated exhausted T cells.Moreover,the progenitor-like precursor cell population may be a subset of T cells that can respond to immunotherapy.Studies have also found that TOX initiates and dominates the development of exhausted T cells at the transcriptional and epigenetic levels.TOX also maintains T cell survival and may affect decisions regarding treatment strategies.In this review,we discuss the latest developments in T cell exhaustion in regards to definitions,subpopulations,development mechanisms,differences in diverse diseases,and treatment prospects for exhausted T cells.Furthermore,we hypothesize that the epigenetic state regulated by TOX might be the key point,which can determine the reversibility of exhaustion and the efficacy of immunotherapy. | Ziqing Zeng Feng Wei Xiubao Ren | 2020 | Cancer Biology & Medicine2020，17，4： | 3 |
| 8 | 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 |
| 9 | Vorolanib,an oral VEGFR/PDGFR dual tyrosine kinase inhibitor for treatment of patients with advanced solid tumors:An open-label,phaseⅠdose escalation and dose expansion trial显示文摘Objective:This study evaluated the safety and preliminary efficacy of vorolanib,a novel tyrosine kinase inhibitor,for treatment of patients with advanced solid tumors.Methods:During dose escalation,patients received increasing doses of oral vorolanib(50-250 mg once daily)in cycles of four weeks for up to one year.During dose expansion,patients received recommended doses(100 and 200 mg)in 4-week cycles.The primary endpoint was to determine the safety and maximum tolerated dose and/or the recommended phase II dose(RP2 D).The severity and type of adverse drug reactions(ADRs)were assessed using the Common Terminology Criteria for Adverse Events version 4.0.The second endpoint was preliminary efficacy in terms of objective response and progression-free survival(PFS).Results:No dose-limiting toxicity occurred during dose escalation(50-250 mg).Five(26.3%)patients in the escalation cohort(n=19)and 12(48.0%)in the expansion cohort(n=25)experienced grade 3 ADRs.The most common ADRs were hair color changes,fatigue,portal hypertension,hypertriglyceridemia,and proteinuria.During dose expansion,the patients treated with 200 mg and 100 mg(once daily)showed an objective response rate of 22.2%and 5.9%,respectively;the disease control rate was 88.9%and 73.3%,respectively;the median PFS was9.9[95%confidence interval(95%CI):7.4-not reached]months and 3.8(95%CI:1.9-not reached)months,respectively.Conclusions:Oral vorolanib at a dose of 200 mg(once daily)exhibited an acceptable safety profile and favorable clinical benefit for patients with advanced solid tumors.The RP2 D for vorolanib was determined to be 200 mg as a daily regimen. | Yan Song Jinwan Wang Xiubao Ren Jie Jin Li Mao Chris Liang Lieming Ding Lin Yang | 2021 | Chinese Journal of Cancer Research2021，33，1： | 2 |
| 10 | Enhanced antitumor effects of DC-activated CIKs to chemotherapy treatment in a single cohort of advanced non-small-cell lung cancer patients显示文摘 | Lili Yang Baozhu Ren Hui Li Jinpu Yu Shui Cao Xishan Hao Xiubao Ren | 2013 | Cancer Immunology Immunotherapy2013，，1： | 2 |
| 11 | Autologous cytokine-induced killer cell immunotherapy in lung cancer: a phase II clinical study显示文摘 | Runmei Li Changli Wang Liang Liu Chunjuan Du Shui Cao Jinpu Yu Shizhen Emily Wang Xishan Hao Xiubao Ren Hui Li | 2012 | Cancer Immunology Immunotherapy2012，，11： | 2 |
| 12 | Can the dual-functional capability of CIK cells be used to improve antitumor effects?显示文摘 | Xiaomeng Wang Wenwen Yu Hui Li Jinpu Yu Xinwei Zhang Xiubao Ren Shui Cao | 2014 | Cellular Immunology2014，，1： | 2 |
| 13 | Insights into tertiary lymphoid structures in the solid tumor microenvironment: anti-tumor mechanism, functional regulation, and immunotherapeutic strategies显示文摘Tertiary lymphoid structures(TLSs)are ectopic immune cell aggregations that develop in peripheral tissues in response to a wide range of chronic inflammatory conditions,including infection,autoimmune disease,and cancer.In the tumor microenvironment(TME),the structures of TLSs,including B-cell-and T-cell-enriched areas indicate that the TLSs might be the local site during the initiation and maintenance of humoral and cellular immune responses against cancers.Numerous studies have evaluated the expression of TLSs in different cancer patients and their association with prognoses of cancer patients.It was shown that welldeveloped TLSs characterized by mature B cells synthesized tumor specific antibodies,which were considered as specific markers for a good prognosis.However,there are still some immunosuppressive factors existing in the TLSs that may affect anti-tumor responses.These factors include dysfunctional B cells,regulatory T cells,and T follicular regulatory cells.The complexity and heterogeneity of the TLS composition may affect the function and activity of TLSs;it is therefore essential to fully understand the function and influencing factors in TLSs.It has been reported that checkpoint inhibitors and vaccines are currently being developed to reprogram the TME by establishing mature TLSs to improve cancer immunotherapies.In this review,we focused on recent advances in TLSs in human solid tumors,including structural characteristics and classes,antitumor mechanisms,immunosuppressive factors,and TLSbased therapeutic approaches. | Hua Zhao Hao Wang Qiuru Zhou Xiubao Ren | 2021 | Cancer Biology & Medicine2021，18，4： | 2 |
| 14 | The prognostic landscape of genes and infiltrating immune cells in cytokine induced killer cell treated-lung squamous cell carcinoma and adenocarcinoma显示文摘Objective:Patients with non–small cell lung cancer(NSCLC)respond differently to cytokine-induced killer cell(CIK)treatment.Therefore,potential prognostic markers to identify patients who would benefit from CIK treatment must be elucidated.The current research aimed at identifying predictive prognostic markers for efficient CIK treatment of patients with NSCLC.Methods:Patients histologically diagnosed with NSCLC were enrolled from the Tianjin Medical University Cancer Institute and Hospital.We performed whole-exome sequencing(WES)on the tumor tissues and paired adjacent benign tissues collected from 50 patients with NSCLC,and RNA-seq on tumor tissues of 17 patients with NSCLC before CIK immunotherapy treatment.Multivariate Cox proportional hazard regression analysis was used to analyze the association between clinical parameters and prognostic relevance.WES and RNA-seq data between lung squamous cell carcinoma(SCC)and adenocarcinoma(Aden)were analyzed and compared.Results:The pathology subtype of lung cancer was the most significantly relevant clinical parameter associated with DFS,as analyzed by multivariate Cox proportional hazard regression(P=0.031).The patients with lung SCC showed better CIK treatment efficacy and extended DFS after CIK treatment.Relatively low expression of HLA class II genes and checkpoint molecules,and less immunosuppressive immune cell infiltration were identified in the patients with lung SCC.Conclusions:Coordinated suppression of the expression of HLA class II genes and checkpoint molecules,as well as less immune suppressive cell infiltration together contributed to the better CIK treatment efficacy in lung SCC than lung Aden. | Jian Wang Fan Yang Qian Sun Ziqing Zeng Min Liu Wenwen Yu Peng Zhang Jinpu Yu Lili Yang Xinwei Zhang Xiubao Ren Feng Wei | 2021 | Cancer Biology & Medicine2021，18，4： | 1 |
| 15 | Morphine-3-glucuronide upregulates PD-L1 expression via TLR4 and promotes the immune escape of non-small cell lung cancer显示文摘Objective:Patients with cancer pain are highly dependent on morphine analgesia,but studies have shown a negative correlation between morphine demand and patient outcomes.The long-term use of morphine may result in abnormally elevated serum morphine-3-glucuronide(M3G)levels.Hence,the effects of M3G on tumor progression are worth studying.Methods:The effects of M3G on PD-L1 expressions in human non-small cell lung cancer(NSCLC)cell lines were first evaluated.Activation of TLR4 downstream pathways after M3G treatment was then determined by Western blot.The effects of M3G on human cytotoxic T lymphocytes(CTL)cytotoxicity and INF-γrelease was also detected.Finally,the LLC murine lung adenocarcinoma cell line were used to establish a murine lung cancer model,and the effects of M3G on tumor growth and metastasis were determined.Results:M3G promoted the expressions of PD-L1 in the A549 and H1299 cell lines in a TLR4-dependent manner(P<0.05).M3G activated the PI3 K and the NFκB signaling pathways,and this effect was antagonized by a TLR4 pathway inhibitor.A PI3 K pathway inhibitor reversed the M3G-mediated PD-L1 upregulation.M3G inhibited the cytotoxicity of CTL on A549 cells and decreased the level of INF-γ.Repeated M3G intraperitoneal injections promoted LLC tumor growth and lung metastasis through the upregulation of tumor expressed PD-L1 and the reduction of CTL in the tumor microenvironment.Conclusions:M3G specifically activated TLR4 in NSCLC cells and upregulated PD-L1 expression through the PI3 K signaling pathway,thereby inhibiting CTL cytotoxicity and finally promoting tumor immune escape. | Kaiyuan Wang Jian Wang Ting Liu Wenwen Yu Nan Dong Chen Zhang Wenbin Xia Feng Wei Lili Yang Xiubao Ren | 2021 | Cancer Biology & Medicine2021，18，1： | 1 |
| 16 | Long noncoding RNA HOTAIR involvement in cancer显示文摘 | Yansheng Wu Li Zhang Yang Wang Hui Li Xiubao Ren Feng Wei Wenwen Yu Xudong Wang Lun Zhang Jinpu Yu Xishan Hao | 2014 | Tumor Biology2014，，10： | 1 |
| 17 | Somatic copy number alterations are predictive of progression-free survival in patients with lung adenocarcinoma undergoing radiotherapy显示文摘Objective:Lung cancer is the most common cause of cancer-related deaths worldwide.Somatic copy number alterations(SCNAs)have been used to predict responses to therapies in many cancers,including lung cancer.However,little is known about whether they are predictive of radiotherapy outcomes.We aimed to understand the prognostic value and biological functions of SCNAs.Methods:We analyzed the correlation between SCNAs and clinical outcomes in The Cancer Genome Atlas data for 486 patients with non-small cell lung cancer who received radiotherapy.Gene set enrichment analyses were performed to investigate the potential mechanisms underlying the roles of SCNAs in the radiotherapy response.Our results were validated in 20 patients with lung adenocarcinoma(LUAD)receiving radiotherapy.Results:SCNAs were a better predictor of progression-free survival(PFS)in LUAD(P=0.024)than in lung squamous carcinoma(P=0.18)in patients treated with radiotherapy.Univariate and multivariate regression analyses revealed the superiority of SCNAs in predicting PFS in patients with LUAD.Patients with stage I cancer and low SCNA levels had longer PFS than those with high SCNA levels(P=0.022).Our prognostic nomogram also showed that combining SCNAs and tumor/node/metastasis provided a better model for predicting long-term PFS.Additionally,high SCNA may activate the cell cycle pathway and induce tumorigenesis.Conclusions:SCNAs may be used to predict PFS in patients with early-stage LUAD with radiotherapy,in combination with TNM,with the aim of predicting long-term PFS.Therefore,SCNAs are a novel predictive biomarker for radiotherapy in patients with LUAD. | Fan Kou Lei Wu Yan Guo Bailu Zhang Baihui Li Ziqi Huang Xiubao Ren Lili Yang | 2022 | Cancer Biology & Medicine2022，19，5： | 1 |
| 18 | Enhanced antitumor effects of DC-activated CIKs to chemotherapy treatment in a single cohort of advanced non-small-cell lung cancer patients显示文摘 | Lili Yang Baozhu Ren Hui Li Jinpu Yu Shui Cao Xishan Hao Xiubao Ren | 2013 | Cancer Immunology, Immunotherapy2013，，1： | 1 |
| 19 | Rosiglitazone Suppresses Glioma Cell Growth and Cell Cycle by Blocking the Transforming Growth Factor-Beta Mediated Pathway显示文摘 | Peng Wang Jinpu Yu Qiang Yin Wenliang Li Xiubao Ren Xishan Hao | 2012 | Neurochemical Research2012，，10： | 1 |
| 20 | 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 |
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