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Predictive biomarkers for immune checkpoint blockade and opportunities for combination therapies

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Genes & Diseases 2019年第3期6卷 232-246页

作者： Hongxing Shen eddy Shih-Hsin Yang Marty Conry John Fiveash Carlo Contreras james A.Bonner Lewis Zhichang Shi Department of Radiation Oncology The University of Alabama at Birmingham School of MedicineBirminghamAL35233USA O’Neal Comprehensive Cancer Center The University of Alabama at Birmingham School of MedicineBirminghamAL35233USA Department of Medical Oncology The University of Alabama at Birmingham School of MedicineBirminghamAL35233USA Department of Surgical Oncology The University of Alabama at Birmingham School of MedicineBirminghamAL35233USA Department of Microbiology The University of Alabama at Birmingham School of MedicineBirminghamAL35233USA Program in Immunology The University of Alabama at Birmingham School of MedicineBirminghamAL35233USA

Immune checkpoint blockade therapies(ICBs)are a prominent breakthrough in cancer immunotherapy in recent years(named the 2013“Breakthrough of the Year”by the Science magazine).Thus far,FDA-approved ICBs primarily target immune checkpoints CTLA-4,PD-1,and PD-L1.Notwithstanding their impressive long-term therapeutic benefits,their efficacy is limited to a small subset of cancer patients.In addition,ICBs induce inadvertent immune-related adverse events(irAEs)and can be costly for long-term use.To overcome these limitations,two strategies are actively being pursued:identification of predictive biomarkers for clinical response to ICBs and multi-pronged combination therapies.Biomarkers will allow clinicians to practice a precision medicine approach in ICBs(biomarker-based patient selection)such as treating triple-negative breast cancer patients that exhibit PD-L1 staining of tumor-infiltrating immune cells in1%of the tumor area with nanoparticle albumin-bound(nab)epaclitaxel plus anti-PD-L1 and treating patients of MSI-H or MMR deficient unresectable or metastatic solid tumors with pembrolizumab(anti-PD-1).Importantly,the insights gained from these biomarker studies can guide rational combinatorial strategies such as CDK4/6 inhibitor/fractionated radiotherapy/HDACi in conjunction with ICBs to maximize therapeutic benefits.Further,with the rapid technological advents(e.g.,ATCT-Seq),we predict more reliable biomarkers will be identified,which in turn will inspire more promising combination therapies.

关键词： IFN-γ Immune checkpoint Microbiota Microsatellite instability Neoantigen PD-L1 Radiotherapy

Development of Model to Predict Vickers Hardness of Hot Rolled 0.028% Nb HSLA Steel

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材料科学与工程（中英文A版） 2013年第3期3卷 200-204页

作者： eddy Sumarno Siradj Dedi Priadi james Handaja Richard Alfonso Mangaraja Napitupulu Metalurgy and Material Engineering Department University of Indonesia Depok 16424 Indonesia Mechanical Engineering Department University of HKBP Nommensen Medan 20234 Indonesia

Model to predict the Vickers hardness of hot-rolled 0.028% Nb hight strength low alloy (HSLA) steel has been developed. Results show that the Vickers hardness is not influenced by the ferrite grain size, but from the dislocation density which, in turn, can be expressed in terms of strain and rolling temperature. These two variables are used to model the Vickers hardness. There is a good agreement between measured and calculated Vickers hardness.

关键词：高强度低合金钢维氏硬度模型预测热卷 HSLA 晶粒尺寸位错密度硬度测量

Atmospheric Precursors of and Response to Anomalous Arctic Sea Ice in CMIP5 Models

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Advances in Atmospheric Sciences 2018年第1期35卷 27-37页

作者： Michael KELLEHER james SCREEN College of Engineering Mathematics and Physical SciencesUniversity of Exeter

This study examines pre-industrial control simulations from CMIP5 climate models in an effort to better understand the complex relationships between Arctic sea ice and the stratosphere, and between Arctic sea ice and cold winter temperatures over Eurasia. We present normalized regressions of Arctic sea-ice area against several atmospheric variables at extended lead and lag times. Statistically significant regressions are found at leads and lags, suggesting both atmospheric precursors of, and responses to, low sea ice; but generally, the regressions are stronger when the atmosphere leads sea ice, including a weaker polar stratospheric vortex indicated by positive polar cap height anomalies. Significant positive midlatitude eddy heat flux anomalies are also found to precede low sea ice. We argue that low sea ice and raised polar cap height are both a response to this enhanced midlatitude eddy heat flux. The so-called "warm Arctic, cold continents" anomaly pattern is present one to two months before low sea ice, but is absent in the months following low sea ice, suggesting that the Eurasian cooling and low sea ice are driven by similar processes. Lastly, our results suggest a dependence on the geographic region of low sea ice, with low Barents–Kara Sea ice correlated with a weakened polar stratospheric vortex, whilst low Sea of Okhotsk ice is correlated with a strengthened polar vortex. Overall, the results support a notion that the sea ice, polar stratospheric vortex and Eurasian surface temperatures collectively respond to large-scale changes in tropospheric circulation.

关键词： sea ice-atmosphere coupling, stratosphere-troposphere coupling, atmospheric circulation, Eurasian climate

Extreme Cold Events from East Asia to North America in Winter 2020/21:Comparisons,Causes,and Future Implications

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Advances in Atmospheric Sciences 2022年第4期39卷 553-565页

作者： Xiangdong ZHANG Yunfei FU Zhe HAN james E.OVERLAND Annette RINKE Han TANG Timo VIHMA Muyin WANG Univeristy of Alaska Fairbanks FairbanksAK 99775USA University of Science and Technology of China Hefei 230026China Institute of Atmospheric Physics Chinese Academy of SciencesBeijing 100029China NOAA/Pacific Marine Environmental Laboratory SeattleWA 98115USA Alfred Wegener Institute Helmholtz Center for Polar and Marine Research14401 PotsdamGermany Finnish Meteorological Institute FI-00101 HelsinkiFinland University of Washington SeattleWA 98105USA

Three striking and impactful extreme cold weather events successively occurred across East Asia and North America during the mid-winter of 2020/21.These events open a new window to detect possible underlying physical processes.The analysis here indicates that the occurrences of the three events resulted from integrated effects of a concurrence of anomalous thermal conditions in three oceans and interactive Arctic-lower latitude atmospheric circulation processes,which were linked and influenced by one major sudden stratospheric warming(SSW).The North Atlantic warm blob initiated an increased poleward transient eddy heat flux,reducing the Barents-Kara seas sea ice over a warmed ocean and disrupting the stratospheric polar vortex(SPV)to induce the major SSW.The Rossby wave trains excited by the North Atlantic warm blob and the tropical Pacific La Nina interacted with the Arctic tropospheric circulation anomalies or the tropospheric polar vortex to provide dynamic settings,steering cold polar air outbreaks.The long memory of the retreated sea ice with the underlying warm ocean and the amplified tropospheric blocking highs from the midlatitudes to the Arctic intermittently fueled the increased transient eddy heat flux to sustain the SSW over a long time period.The displaced or split SPV centers associated with the SSW played crucial roles in substantially intensifying the tropospheric circulation anomalies and moving the jet stream to the far south to cause cold air outbreaks to a rarely observed extreme state.The results have significant implications for increasing prediction skill and improving policy decision making to enhance resilience in“One Health,One Future”.

关键词： extreme weather events sea surface temperature Arctic sea ice Arctic amplification sudden stratospheric warming stratospheric polar vortex

A 10-miRNA risk score-based prediction model for pathological complete response to neoadjuvant chemotherapy in hormone receptor-positive breast cancer

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Science China(Life Sciences) 2022年第11期65卷 2205-2217页

作者： Chang Gong Ziliang Cheng Yaping Yang Jun Shen Yingying Zhu Li Ling Wanyi Lin Zhigang Yu Zhihua Li Weige Tan Chushan Zheng Wenbo Zheng Jiajie Zhong Xiang Zhang Yunjie Zeng Qiang Liu RStephanie Huang Andrzej LKomorowski eddy SYang François Bertucci Francesco Ricci Armando Orlandi Gianluca Franceschini Kazuaki Takabe Suzanne Klimberg Naohiro Ishii Angela Toss Mona PTan Mathew A Cherian Erwei Song Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Guangdong-Hong Kong Joint Laboratory for RNA MedicineBreast Tumor CenterSun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Department of Radiology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Clinical Research Design Division Clinical Research CenterSun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Department of Medical Statistics School of Public HealthSun Yat-sen UniversityGuangzhou 510080China Department of Breast Surgery the Second Affiliated HospitalShandong UniversityJinan 250033China Department of Breast Surgery Key Laboratory of Breast DiseasesThird Hospital of NanchangNanchang 330009China Department of Breast Surgery the First Affiliated HospitalGuangzhou Medical UniversityGuangzhou 510120China Department of Pathology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Department of Experimental and Clinical Pharmacology University of MinnesotaMinneapolisMN 55455USA Department of Surgery College of MedicineUniversity of RzeszówRzeszów 35-959Poland Department of Radiation Oncology O’Neal Comprehensive Cancer CenterUniversity of Alabama at Birmingham School of MedicineBirminghamALUSA Laboratoty of Predictive Oncology Institut Paoli-CalmettesCentre de Recherche en Cancérologie de MarseilleINSERM UMR1068CNRS UMR725MarseilleFrance Department of Drug Development and Innovation(D3i) Institut CurieParis 75005France Comprehensive Cancer Center UOC di Oncologia MedicaFondazione Policlinico Universitario A.Gemelli IRCCSRome 00168Italy Multidisciplinary Breast Unit Fondazione Policlinico Universitario Agostino Gemelli IRCCSUniversitàCattolica del Sacro CuoreRome 00168Italy Breast Surgery Department of Surgical OncologyRoswell Park Comprehensive Cancer CenterBuffaloNYUSA Department of Surgery MD Anderson Cancer CenterHoustonTX 77030USA Department of Plastic and Reconstructive Surgery

Patients with hormone receptor(HR)-positive tumors breast cancer usually experience a relatively low pathological complete response(p CR)to neoadjuvant chemotherapy(NAC).Here,we derived a 10-micro RNA risk score(10-mi RNA RS)-based model with better performance in the prediction of p CR and validated its relation with the disease-free survival(DFS)in 755 HRpositive breast cancer patients(273,265,and 217 in the training,internal,and external validation sets,respectively).This model,presented as a nomogram,included four parameters:the 10-mi RNA RS found in our previous study,progesterone receptor(PR),human epidermal growth factor receptor 2(HER2)status,and volume transfer constant(K).Favorable calibration and discrimination of 10-mi RNA RS-based model with areas under the curve(AUC)of 0.865,0.811,and 0.804 were shown in the training,internal,and external validation sets,respectively.Patients who have higher nomogram score(>92.2)with NAC treatment would have longer DFS(hazard ratio=0.57;95%CI:0.39–0.83;P=0.004).In summary,our data showed the 10-mi RNA RS-based model could precisely identify more patients who can attain p CR to NAC,which may help clinicians formulate the personalized initial treatment strategy and consequently achieves better clinical prognosis for patients with HRpositive breast cancer.

关键词： hormone receptor-positive breast cancer micro RNA signature neoadjuvant chemotherapy dynamic contrast-enhanced magnetic resonance imaging nomogram