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High baseline tumor burden-associated macrophages promote an immunosuppressive microenvironment and reduce the efficacy of immune checkpoint inhibitors through the IGFBP2-STAT3-PD-L1 pathway

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Cancer Communications 2023年第5期43卷 562-581页

作者： Zhaowei Wen Huiying Sun Zhihua Zhang Yannan Zheng Siting Zheng Jianping Bin Yulin Liao Min Shi Rui Zhou Wangjun Liao Department of Oncology Nanfang HospitalSouthern Medical UniversityGuangzhou510515GuangdongP.R.China Department of Cardiology Nanfang HospitalSouthern Medical UniversityGuangzhou510515GuangdongP.R.China

Background:Several clinical studies have uncovered a negative correlation between baseline tumor burden and the efficacy of immune checkpoint inhibitor(ICI)*** study aimed to uncover the specific mechanisms underlying the difference in sensitivity to ICI treatment between tumors with high(HTB)and low(LTB)tumor ***:For in vivo studies,several mouse models of subcutaneous tumors were established,and transcriptome sequencing,immunohistochemistry,and flow cytometry assays were used to detect the immune status in these subcutaneous *** in vitro experiments,co-culture models,cytokine antibody arrays,western blotting,flow cytometry,and enzyme-linked immunosorbent assays were used to explore the underlying molecular mechanisms Results:We found that MC38 or B16 subcutaneous tumors from the HTB group did not show any response to anti-programmed cell death protein-1(PD-1)*** flow cytometry assays,we found that the infiltration with CD8^(+)T cellswas significantly decreasedwhereasM2-like macrophageswere enriched in subcutaneous tumors of HTB groups compared with those of LTB *** changes were not affected by the initial number of injected tumor cells or tumor age,nor could they be reversed by surgical tumor *** colony-stimulating factor 1 receptor(CSF-1R)inhibitor PLX3397 injection at different time points of tumor growth only had an effect when administered in the early tumor stage to maintain the“heat”of the tumor microenvironment during the process of tumor growth,thereby achieving a response to ICI treatment when the tumor grew to a large ***,we found that insulin-like growth factor binding protein 2(IGFBP2)expression levelswere significantly elevated in HTB tumor ***2 promoted the programmed death-ligand 1(PD-L1)expression in M2-like macrophages by activating signal transducer and activator of transcription 3(STAT3),and PD-L1^(+)M2-likemacrophages exerted an immunosuppressive e

关键词： CD8^(+)T cell IGFBP2 immune checkpoint inhibitor macrophage PD-L1 STAT3 tumor burden tumor immune microenvironment

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The size of cell-free mitochondrial DNA in blood is inversely correlated with tumor burden in cancer patients

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Precision Clinical Medicine 2019年第3期2卷 131-139页

作者： Qin An Youjin Hu Qingjiao Li Xufeng Chen Jiaoti Huang Matteo Pellegrini Xianghong Jasmine Zhou Matthew Rettig Guoping Fan Department of Human Genetics David Geffen School of MedicineUniversity of California Los AngelesLos AngelesCA 90095USA Department of Pathology and Laboratory Medicine David Geffen School of MedicineUniversity of California Los AngelesLos AngelesCA 90095USA Department of Pathology Duke University School of MedicineDurhamNC 27710USA Department of Molecular Celland Developmental BiologyUniversity of California Los AngelesLos AngelesCA 90095-7239USA and 5Department of Urology David Geffen School of MedicineUniversity of California Los AngelesLos AngelesCA 90095USA

Circulating cell-free DNAs(cfDNAs)are fragmented DNA molecules released into the blood by *** studies have suggested that mitochondria-originated cfDNA fragments(mt-cfDNAs)in cancer patients are more fragmented than those from healthy ***,it is still unknown where these short mtcfDNAs originate,and whether the length of mt-cfDNAs can be correlated with tumor burden and cancer *** this study,we first performed whole-genome sequencing analysis(WGS)of cfDNAs from a human tumor cell line-xenotransplantation mouse model and found that mt-cfDNAs released from transplanted tumor cells were shorter than the mouse *** next analyzed blood cfDNA samples from hepatocellular carcinoma and prostate cancer patients and found that mt-cfDNA lengths were inversely related to tumor size as well as the concentration of circulating tumor *** study suggested that monitoring the size of mt-cfDNAs in cancer patients would be a useful way to estimate tumor burden and cancer progression.

关键词： circulating cell-free DNA(cfDNA) tumor burden cancer progression liquid biopsy

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Predictive function of tumor burden-incorporated machine-learning algorithms for overall survival and their value in guiding management decisions in patients with locally advanced nasopharyngeal carcinoma

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Journal of the National Cancer Center 2023年第4期3卷 295-305页

作者： Yang Liu Shiran Sun Ye Zhang Xiaodong Huang Kai Wang Yuan Qu Xuesong Chen Runye Wu Jianghu Zhang Jingwei Luo Yexiong Li Jingbo Wang Junlin Yi Department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Hebei Cancer HospitalChinese Academy of Medical Sciences(CAMS)Langfang 065001China

Objective:Accurate prognostic predictions and personalized decision-making on induction chemotherapy(IC)for individuals with locally advanced nasopharyngeal carcinoma(LA-NPC)remain *** research examined the predictive function of tumor burden-incorporated machine-learning algorithms for overall survival(OS)and their value in guiding treatment in patients with ***:Individuals with LA-NPC were reviewed *** burden signature-based OS prediction models were established using a nomogram and two machine-learning methods,the interpretable eXtreme Gradi-ent Boosting(XGBoost)risk prediction model,and DeepHit time-to-event neural *** models’prediction performances were compared using the concordance index(C-index)and the area under the curve(AUC).The patients were divided into two cohorts based on the risk predictions of the most successful *** efficacy of IC combined with concurrent chemoradiotherapy was compared to that of chemoradiotherapy ***:The 1221 eligible individuals,assigned to the training(n=813)or validation(n=408)set,showed significant respective differences in the C-indices of the XGBoost,DeepHit,and nomogram models(0.849 and 0.768,0.811 and 0.767,0.730 and 0.705).The training and validation sets had larger AUCs in the XGBoost and DeepHit models than the nomogram model in predicting OS(0.881 and 0.760,0.845 and 0.776,and 0.764 and 0.729,Ptumor burden with clinical variables to predict OS and determine which patients will most likely gain from *** model could be valuable for delivering patient counseling and conducting clinical evaluations.

关键词： Nasopharyngeal carcinoma Machine learning tumor burden Prognostic model Induction chemotherapy

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Effect of serum testosterone and percent tumor volume on extra-prostatic extension and biochemical recurrence after laparoscopic radical prostatectomy

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Asian Journal of Andrology 2016年第1期18卷 54-59页

作者： Eu Chang Hwang Seong Hyeon Yu Yang Hyun Jo Seung I1 Jung Taek Won Kang Dong Deuk Kwon Chan Choi Suk Hee Heo Jun Eul Hwang Sung-Hoon Jung Tae-Young Jung Department of Urology Chonnam National University Medical School Gwangju Republic of Korea Department of Pathology Chonnam National University Medical School Gwangju Republic of Korea Department of Radiology Chonnam National University Medical School Gwangju Republic of Korea Department of Hemato-oncology Chonnam National University Medical School Gwangju Republic of Korea Department of Neurosurgery Chonnam National University Medical Schoo Gwangju Republic of Korea

Several studies have revealed that the preoperative serum testosterone and percent tumor volume （PTV） predict extra-prostatic extension （EPE） and biochemical recurrence （BCR） after radical prostatectomy. This study investigated the prognostic significance of serum testosterone and PTV in relation to EPE and BCR after laparoscopic radical prostatectomy （LRP）. We reviewed 520 patients who underwent LRP between 2004 and 2012. PTV was determined as the sum of all visually estimated tumor foci in every section. BCR was defined as two consecutive increases in the postoperative prostate-specific antigen （PSA）〉0.2 ng ml^-1. The threshold for serum total testosterone was 3.0 ng ml^-1, Multivariate logistic regression was used to define the effect of variables on the risk of EPE and BCR. A low serum testosterone （〈3.0 ng ml^-1） was associated with a high serum PSA, Gleason score, positive core percentage of the prostate biopsy, PTV, and all pathological variables. On multivariate analysis, similar to previous studies, the serum PSA, biopsy positive core percentage, Gleason score, and pathological variables predicted EPE and BCR. In addition, low serum testosterone （〈3.0 ng ml^-1, adjusted OR, 8.52; 95% CI, 5.04-14.4, P = 0.001） predicted EPE and PTV （adjusted OR, 1.02; 95% CI, 1.01-1.05, P = 0.046） predicted BCR. In addition to previous predictors of EPE and BCR, low serum testosterone and PTV are valuable predictors of EPE and BCR after LRP.

关键词： biochemical recurrence extra-prostatic extension prostate neoplasms prostatectomy testosterone tumor burden

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Liver Transplantation Beyond Milan Criteria

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Journal of Clinical and Translational Hepatology 2020年第1期8卷 69-75页

作者： Vivek A Lingiah Mumtaz Niazi Raquel Olivo Flavio Paterno James V Guarrera Nikolaos T Pyrsopoulos Department of Medicine Division of Gastroenterology and HepatologyRutgers UniversityNew Jersey Medical SchoolNewarkNJUSA Department of Surgery Division of Liver Transplantation and Hepatobiliary SurgeryRutgers UniversityNew Jersey Medical SchoolNewarkNJUSA

Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-related death worldwide,being the fifth most common cancer and the third most common cause of cancer-related *** incidence of HCC has been rising in the USA over the last 20 *** transplanta-tion is an optimal treatment option,as it eliminates HCC as well as the underlying liver *** Milan criteria(1 lesion greater than or equal to 2 cm and less than or equal to 5 cm,or up to 3 lesions,each greater than or equal to 1 cm and less than or equal to 3 cm)have been adopted by many transplant societies worldwide as the criteria to determine whether patients with HCC can move forward with liver ***,many believe that the Milan criteria may be too strict in regard to its size require-ments for *** has led to a number of expanded criteria for liver transplantation,concerning both overall size and number of lesions,as well as incorporation of other markers of tumor *** markers,such as alpha-fetoprotein,can also be used to follow treatment of HCC and possibly exclude patients from *** presenting beyond Milan criteria can also be down-staged with locore-gional *** response to locoregional therapy and longer wait times after locoregional therapy prior to transplant can serve as surrogate markers of tumor biology as well.

关键词： Hepatocellular carcinoma Liver transplantation Cancer staging tumor burden Alpha-fetoprotein

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Hypothetical hypoxia-driven rapid disease progression in hepatocellular carcinoma post transarterial chemoembolization:A case report

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World Journal of Clinical Cases 2023年第19期11卷 4664-4669页

作者： Kai-Fuan Yeo Amy Ker Pei-En Kao Chi-Chih Wang Division of Gastroenterology and Hepatology Department of Internal MedicineChung Shan Medical University HospitalTaichung 402306Taiwan China School of Medicine Chung Shan Medical UniversityTaichung 402306TaiwanChina

BACKGROUND Transarterial chemoembolization(TACE)is widely performed for intermediatestage or unresectable hepatocellular carcinoma(HCC),but approximately half of patients do not respond to TACE *** describe a case of rapidly progressing of HCC after TACE and provide a possible hypothesis for this *** finding may contribute to identifying patients who obtain less benefit from TACE,thus avoiding the unnecessary waste of medical resources and treatment during the golden hour *** SUMMARY A 61-year-old woman had been diagnosed with chronic hepatitis B infection and HCC at Barcelona Clinic Liver Cancer stage B,which had been treated by segmental hepatectomy 14 mo *** tumor recurred in the two months after *** received an initial TACE and then underwent systemic therapy with lenvatinib 8 mg daily due to an increased level of alpha-fetoprotein(AFP)after the first ***,the tumor continued to progress with an increased level of AFP,and she underwent a second TACE,after which the tumor volume did not obviously decrease on the contrast-enhanced computed tomography *** month later,she had a third TACE to control the residual HCC *** weeks after that,the HCC had increased dramatically with tea-colored urine and yellowish skin ***,the patient refused further treatment and went into hospice *** Intense hypoxia induced by TACE can trigger rapid disease progression in infiltrative HCC patients with a large tumor burden.

关键词： Carcinoma hepatocellular Transarterial chemoembolization tumor hypoxia Disease progression tumor burden Case report

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Intermittent androgen deprivation therapy in patients with prostate cancer: Connecting the dots

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Asian Journal of Urology 2017年第4期4卷 208-222页

作者： Per-Anders Abrahamsson Department of Urology Skane University HospitalLund UniversityMalmooSweden

Intermittent androgen deprivation therapy(IADT)is now being increasingly opted by the treating physicians and patients with prostate *** most common reason driving this is the availability of an off-treatment period to the patients that provides some relief from treatment-related side-effects,and reduced treatment *** may also delay the progression to castration-resistant prostate ***,the use of IADT in the setting of prostate cancer has not been strongly substantiated by data from clinical *** factors seem to contribute towards this inadequacy of supportive data for the use of IADT in patients with prostate cancer,e.g.,population characteristics(both demographic and clinical),study design,treatment regimen,on-and off-treatment criteria,duration of active treatment,endpoints,and *** present review article focuses on seven clinical trials that evaluated the efficacy of IADT *** androgen deprivation therapy for the treatment of prostate *** results from these clinical trials have been discussed in light of the factors that may impact the treatment outcomes,especially the disease(tumor)*** on evidence,potential candidate population for IADT has been suggested along with recommendations for the use of IADT in patients with prostate cancer.

关键词： Continuous androgen deprivation therapy Intermittent androgen deprivation therapy Prostate cancer Study designs and outcomes tumor burden

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Socioeconomic inequalities in cancer incidence and mortality:An analysis of GLOBOCAN 2022

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Chinese Medical Journal 2024年第12期137卷 1407-1413页

作者： Wei Cao Kang Qin Feng Li Wanqing Chen Office of Cancer Screening National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Hangzhou Center for Disease Control and Prevention HangzhouZhejiang 310021China The Third People’s Hospital of Xiaoshan HangzhouZhejiang 311251China

Background:Given the recent updates in cancer burden estimates by GLOBOCAN 2022,this study was undertaken to provide pertinent perspectives within the context of the Human Development Index(HDI)and major world ***:Datasets sourced from GLOBOCAN encompassed cancer cases and deaths across all cancer types in 2022,alongside projections up to *** incidences and deaths of the top 10 cancers within China and four distinct HDI-classified regions were compared using descriptive ***-standardized incidence rates(ASIRs)and mortality rates(ASMRs)worldwide for the most prevalent cancers in 2022 across ten largest economies and four-tier HDIs were *** top five cancer types concerning both incidence and mortality in China were delineated by sex and age ***:In males,prostate cancer predominated in countries with low,high(except China),and very high *** and liver cancers were prominent causes of death in countries with low *** females,breast and cervical cancers predominated in countries with low-to-medium *** and colorectal cancer incidence and deaths increased with high HDI for both *** and ASMRs for breast,prostate,lung,and colorectal cancers in the top 10 economies were higher than the global ***,liver,stomach,and cervical cancers in most Western countries exhibited lower *** China,hematologic malignancies(43%)were prevalent among children aged 0-14 years,whereas thyroid cancer led among adolescents and young adults aged 15-39 *** incidence and mortality,lung cancer predominated for individuals over 40 years,except for females aged 40-59 years,in whom breast cancer *** trends indicated substantial increases in new cancer cases(76.6%)and deaths(89.7%)over the next three ***:Infection-and poverty-related cancer burdens are offset by increased prostate,breast,colorectal,and lung cancer incidence associated with rapid societal and economic transi

关键词： Incidence Mortality tumor burden China Human Development Index Hematologic neoplasms Lung neoplasms Breast neoplasms Colorectal neoplasms Thyroid neoplasms Liver neoplasms Prostatic neoplasms Early detection of cancer

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