Digital Commons Network^™

Erratum: Cxcl12-Mediated Monocyte Transmigration Into Brain Perivascular Space Leads To Neuroinflammation And Memory Deficit In Neuropathic Pain, Chun-Lin Mai, Zhi Tan, Ya-Nan Xu, Jing-Jun Zhang, Zhen-Hua Huang, Dong Wang, Hui Zhang, Wen-Shan Gui, Jun Zhang, Zhen-Jia Lin, Ying-Tong Meng, Xiao Wei, Ying-Tao Jie, Peter M Grace, Long-Jun Wu, Li-Jun Zhou, Xian-Guo Liu

Faculty, Staff and Student Publications

In the original Figure 7E of our article, the authors mistakenly reused the GFAP immunostaining representative image of the Vehi+Sham group for the anti-CXCL12+Sham group. This is because an error occurred in converting the original purple fluorescence of GFAP for each group to red fluorescence during preparation of representative pictures of Figure 7E. Unfortunately, this error was not found in multiple revisions. The correct version of Figure 7E is shown below. The correction made in this Erratum does not affect the results and conclusions in this study. The authors apologize for any inconvenience the errors may have caused.

Late Effects Of Craniospinal Irradiation Using Electron Spinal Fields For Pediatric Patients With Cancer, Brian De, Marcus A Florez, Ethan B Ludmir, Moshe H Maor, Susan L Mcgovern, Mary Frances Mcaleer, David R Grosshans, Eric L Chang, Anita Mahajan, Arnold C Paulino

Faculty, Staff and Student Publications

Purpose: For children, craniospinal irradiation (CSI) with photons is associated with significant toxic effects. The use of electrons for spinal fields is hypothesized to spare anterior structures but the long-term effects remain uncertain. We studied late effects of CSI using electrons for spinal radiation therapy (RT).

Methods and materials: Records of 84 consecutive patients treated with CSI using electrons for the spine at a single institution between 1983 and 2014 were reviewed. Median age at RT was 5 (range, 1-14) years. The most common histologies were medulloblastoma/primitive neuroectodermal tumor (59%) and ependymoma (8%). The median prescribed dose to the entire …

Protective Role Of Colitis In Inflammatory Arthritis Via Propionate-Producing Bacteroides In The Gut, Hoh-Jeong Shon, Yu-Mi Kim, Kyeong Seog Kim, Jin-Ouk Choi, Sang-Hyun Cho, Sujin An, Se-Hyeon Park, Yong-Joon Cho, Joo-Hong Park, Sang-Uk Seo, Joo-Youn Cho, Wan-Uk Kim, Donghyun Kim

Faculty, Staff and Student Publications

OBJECTIVES: To investigate whether and how inflammatory disease in the intestine influences the development of arthritis, considering that organ-to-organ communication is associated with many physiological and pathological events.

METHODS: First, mice were given drinking water containing dextran sodium sulfate (DSS) and then subjected to inflammatory arthritis. We compared the phenotypic symptoms between the cohoused and separately-housed mice. Next, donor mice were divided into DSS-treated and untreated groups and then cohoused with recipient mice. Arthritis was then induced in the recipients. The fecal microbiome was analyzed by 16S rRNA amplicon sequencing. We obtained type strains of the candidate bacteria and generated …

Accurate Prediction Of Functional Effect Of Single Amino Acid Variants With Deep Learning, Houssemeddine Derbel, Zhongming Zhao, Qian Liu

Faculty, Staff and Student Publications

The assessment of functional effect of amino acid variants is a critical biological problem in proteomics for clinical medicine and protein engineering. Although natively occurring variants offer insights into deleterious variants, high-throughput deep mutational experiments enable comprehensive investigation of amino acid variants for a given protein. However, these mutational experiments are too expensive to dissect millions of variants on thousands of proteins. Thus, computational approaches have been proposed, but they heavily rely on hand-crafted evolutionary conservation, limiting their accuracy. Recent advancement in transformers provides a promising solution to precisely estimate the functional effects of protein variants on high-throughput experimental data. …

Optimal Ranking And Directional Signature Classification Using The Integral Strategy Of Multi-Objective Optimization-Based Association Rule Mining Of Multi-Omics Data, Saurav Mallik, Soumita Seth, Amalendu Si, Tapas Bhadra, Zhongming Zhao

Faculty, Staff and Student Publications

No abstract provided.

3pnmf-Mkl: A Non-Negative Matrix Factorization-Based Multiple Kernel Learning Method For Multi-Modal Data Integration And Its Application To Gene Signature Detection\, Saurav Mallik, Anasua Sarkar, Sagnik Nath, Ujjwal Maulik, Supantha Das, Soumen Kumar Pati, Soumadip Ghosh, Zhongming Zhao

Faculty, Staff and Student Publications

In this current era, biomedical big data handling is a challenging task. Interestingly, the integration of multi-modal data, followed by significant feature mining (gene signature detection), becomes a daunting task. Remembering this, here, we proposed a novel framework, namely, three-factor penalized, non-negative matrix factorization-based multiple kernel learning with soft margin hinge loss (3PNMF-MKL) for multi-modal data integration, followed by gene signature detection. In brief, limma, employing the empirical Bayes statistics, was initially applied to each individual molecular profile, and the statistically significant features were extracted, which was followed by the three-factor penalized non-negative matrix factorization method used for data/matrix fusion …

Predictive Modeling Using Shape Statistics For Interpretable And Robust Quality Assurance Of Automated Contours In Radiation Treatment Planning, Zachary T Wooten, Cenji Yu, Laurence E Court, Christine B Peterson

Faculty, Staff and Student Publications

Deep learning methods for image segmentation and contouring are gaining prominence as an automated approach for delineating anatomical structures in medical images during radiation treatment planning. These contours are used to guide radiotherapy treatment planning, so it is important that contouring errors are flagged before they are used for planning. This creates a need for effective quality assurance methods to enable the clinical use of automated contours in radiotherapy. We propose a novel method for contour quality assurance that requires only shape features, making it independent of the platform used to obtain the images. Our method uses a random forest …

Evolutionary Aspects Of Infections: Inflammation And Sickness Behaviors, Robert Dantzer

Faculty, Staff and Student Publications

Sickness behavior was conceptualized initially as the behavioral counterpart of the fever response to infectious pathogens. It helps to raise body temperature to its higher setpoint and to maintain it at this new level and it has the additional benefit of enabling a weakened organism to protect itself from other dangers. The discovery of the behavioral effects of proinflammatory cytokines produced by activated immune cells provided a cellular and molecular basis to this phenomenon. The administration of cytokines or cytokine inducers like lipopolysaccharide to healthy rodents allowed to reveal the similarities and differences between inflammation-induced sickness behavior and the fever …

Inhibition Of Nox2 Or Nlrp3 Inflammasome Prevents Cardiac Remote Ischemic Preconditioning, Sandra Benavides, Rodrigo Palavecino, Jaime A Riquelme, Luis Montecinos, José Pablo Finkelstein, Paulina Donoso, Gina Sánchez

Faculty, Staff and Student Publications

Introduction: Short episodes of ischemia-reperfusion (IR) in the heart (classical ischemic preconditioning, IPC) or in a limb (remote ischemic preconditioning, RIPC) before a prolonged ischemic episode, reduce the size of the infarct. It is unknown whether IPC and RIPC share common mechanisms of protection. Animals KO for NOX2, a superoxide-producing enzyme, or KO for NLRP3, a protein component of inflammasome, are not protected by IPC. The aim of this study was to investigate if NOX2 or NLRP3 inflammasome are involved in the protection induced by RIPC. Methods: We preconditioned rats using 4 × 5 min periods of IR in the …

Targeting Mcl-1 Protein To Treat Cancer: Opportunities And Challenges, Shady I Tantawy, Natalia Timofeeva, Aloke Sarkar, Varsha Gandhi

Faculty, Staff and Student Publications

Evading apoptosis has been linked to tumor development and chemoresistance. One mechanism for this evasion is the overexpression of prosurvival B-cell lymphoma-2 (BCL-2) family proteins, which gives cancer cells a survival advantage. Mcl-1, a member of the BCL-2 family, is among the most frequently amplified genes in cancer. Targeting myeloid cell leukemia-1 (MCL-1) protein is a successful strategy to induce apoptosis and overcome tumor resistance to chemotherapy and targeted therapy. Various strategies to inhibit the antiapoptotic activity of MCL-1 protein, including transcription, translation, and the degradation of MCL-1 protein, have been tested. Neutralizing MCL-1's function by targeting its interactions …

Reactome Pathway Analysis From Whole-Blood Transcriptome Reveals Unique Characteristics Of Systemic Sclerosis Patients At The Preclinical Stage, Chiara Bellocchi, Xuan Wang, Marka A Lyons, Maurizio Marchini, Maurizio Lorini, Vincenzo Carbonelli, Nicola Montano, Shervin Assassi, Lorenzo Beretta

Faculty, Staff and Student Publications

OBJECTIVE: This study aims to characterize differential expressed pathways (DEP) in subjects with preclinical systemic sclerosis (PreSSc) characterized uniquely by Raynaud phenomenon, specific autoantibodies, and/or capillaroscopy positive for scleroderma pattern.

METHODS: Whole-blood samples from 33 PreSSc with clinical prospective data (baseline and after 4 years of follow-up) and 16 matched healthy controls (HC) were analyzed for global gene expression transcriptome analysis via RNA sequencing. Functional Analysis of Individual Microarray Expression method annotated Reactome individualized pathways. ANOVA analysis identified DEP whose predictive capability were tested in logistic regression models after extensive internal validation.

RESULTS: At 4 years, 42.4% subjects progressed (evolving …

The Rising Tide Of Revisional Surgery: Tracking Changes In Index Cases Among Bariatric-Accredited Fellowships, Lincoln N Strickland, Erika Y Faraoni, Wei Ruan, Xiaoyi Yuan, Holger K Eltzschig, Jennifer M Bailey-Lundberg

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense desmoplastic stroma that impedes drug delivery, reduces parenchymal blood flow, and suppresses the anti-tumor immune response. The extracellular matrix and abundance of stromal cells result in severe hypoxia within the tumor microenvironment (TME), and emerging publications evaluating PDAC tumorigenesis have shown the adenosine signaling pathway promotes an immunosuppressive TME and contributes to the overall low survival rate. Hypoxia increases many elements of the adenosine signaling pathway, resulting in higher adenosine levels in the TME, further contributing to immune suppression. Extracellular adenosine signals through 4 adenosine receptors (Adora1, Adora2a, Adora2b, Adora3). Of …

Chronic Restraint Stress Impairs Voluntary Wheel Running But Has No Effect On Food-Motivated Behavior In Mice, Kiersten Scott, Thien Trong Phan, Nabila Boukelmoune, Cobi J Heijnen, Robert Dantzer

Faculty, Staff and Student Publications

Chronic restraint stress is known to cause significant alterations of mitochondrial biology. However, its effects on effort-based behavior and the sensitivity of these effects to treatments that restore mitochondrial function have not been assessed. Based on the hypothesis that the behavioral consequences of this stressor should be more severe for an energy demanding activity than for an energy procuring activity, we compared the effects of chronic restraint stress on the performance of male mice trained to use a running wheel or to nose poke for a food reward in an operant conditioning cage. In accordance with our hypothesis, we observed …

Henry Gas Solubility Optimization Double Machine Learning Classifier For Neurosurgical Patients, Diana T Mosa, Amena Mahmoud, John Zaki, Shaymaa E Sorour, Shaker El-Sappagh, Tamer Abuhmed

Faculty, Staff and Student Publications

This study aims to predict head trauma outcome for Neurosurgical patients in children, adults, and elderly people. As Machine Learning (ML) algorithms are helpful in healthcare field, a comparative study of various ML techniques is developed. Several algorithms are utilized such as k-nearest neighbor, Random Forest (RF), C4.5, Artificial Neural Network, and Support Vector Machine (SVM). Their performance is assessed using anonymous patients' data. Then, a proposed double classifier based on Henry Gas Solubility Optimization (HGSO) is developed with Aquila optimizer (AQO). It is implemented for feature selection to classify patients' outcome status into four states. Those are mortality, morbidity, …

Radiographic Response To Neoadjuvant Therapy In Pleural Mesothelioma Should Serve As A Guide For Patient Selection For Cytoreductive Operations, Nathaniel Deboever, Nicolas Zhou, Daniel J Mcgrail, Katarzyna Tomczak, Jacqueline L Oliva, Hope A Feldman, Edwin Parra, Jianjun Zhang, Percy P Lee, Mara B Antonoff, Wayne L Hofstetter, Reza J Mehran, Ravi Rajaram, David C Rice, Jack A Roth, Stephen S Swisher, Ara A Vaporciyan, Mehmet Altan, Annikka Weissferdt, Anne S Tsao, Cara L Haymaker, Boris Sepesi

Faculty, Staff and Student Publications

BACKGROUND: Malignant pleural mesothelioma (MPM) is associated with poor prognosis despite advances in multimodal therapeutic strategies. While patients with resectable disease may benefit from added survival with oncologic resection, patient selection for mesothelioma operations often relies on both objective and subjective evaluation metrics. We sought to evaluate factors associated with improved overall survival (OS) in patients with mesothelioma who underwent macroscopic complete resection (MCR).

METHODS: Patients with MPM who received neoadjuvant therapy and underwent MCR were identified in a prospectively maintained departmental database. Clinicopathologic, blood-based, and radiographic variables were collected and included in a Cox regression analysis (CRA). Response to …

Possible Molecular Mechanisms Underlying The Development Of Atherosclerosis In Cancer Survivors, Priyanka Banerjee, Julia Enterría Rosales, Khanh Chau, Minh T H Nguyen, Sivareddy Kotla, Steven H Lin, Anita Deswal, Robert Dantzer, Elizabeth A Olmsted-Davis, Hung Nguyen, Guangyu Wang, John P Cooke, Jun-Ichi Abe, Nhat-Tu Le

Faculty, Staff and Student Publications

Cancer survivors undergone treatment face an increased risk of developing atherosclerotic cardiovascular disease (CVD), yet the underlying mechanisms remain elusive. Recent studies have revealed that chemotherapy can drive senescent cancer cells to acquire a proliferative phenotype known as senescence-associated stemness (SAS). These SAS cells exhibit enhanced growth and resistance to cancer treatment, thereby contributing to disease progression. Endothelial cell (EC) senescence has been implicated in atherosclerosis and cancer, including among cancer survivors. Treatment modalities for cancer can induce EC senescence, leading to the development of SAS phenotype and subsequent atherosclerosis in cancer survivors. Consequently, targeting senescent ECs displaying the SAS …

Chimeric Rnas Reveal Putative Neoantigen Peptides For Developing Tumor Vaccines For Breast Cancer, Brandon Mistretta, Sakuni Rankothgedera, Micah Castillo, Mitchell Rao, Kimberly Holloway, Anjana Bhardwaj, Maha El Noafal, Constance Albarracin, Randa El-Zein, Hengameh Rezaei, Xiaoping Su, Rehan Akbani, Xiaoshan M Shao, Brian J Czerniecki, Rachel Karchin, Isabelle Bedrosian, Preethi H Gunaratne

Faculty, Staff and Student Publications

INTRODUCTION: We present here a strategy to identify immunogenic neoantigen candidates from unique amino acid sequences at the junctions of fusion proteins which can serve as targets in the development of tumor vaccines for the treatment of breastcancer.

METHOD: We mined the sequence reads of breast tumor tissue that are usually discarded as discordant paired-end reads and discovered cancer specific fusion transcripts using tissue from cancer free controls as reference. Binding affinity predictions of novel peptide sequences crossing the fusion junction were analyzed by the MHC Class I binding predictor, MHCnuggets. CD8+ T cell responses against the 15 peptides were …

The Importance Of "When" In Calorie Restriction-Induced Lifespan Extension, Kristin Eckel-Mahan

Faculty, Staff and Student Publications

No abstract provided.

Targeted Genomic Sequencing Of Tsc1 And Tsc2 Reveals Causal Variants In Individuals For Whom Previous Genetic Testing For Tuberous Sclerosis Complex Was Normal, Hannah D West, Mark Nellist, Rutger W W Brouwer, Mirjam C G N Van Den Hout-Van Vroonhoven, Luiz Gustavo Dufner De Almeida, Femke Hendriks, Peter Elfferich, Meera Raja, Peter Giles, Rosa M Alfano, Angela Peron, Yves Sznajer, Liesbeth De Waele, Anna Jansen, Marije Koopmans, Anneke Kievit, Laura S Farach, Hope Northrup, Julian R Sampson, Laura E Thomas, Wilfred F J Van Ijcken

Faculty, Staff and Student Publications

Tuberous sclerosis complex (TSC) is caused by inactivating variants in TSC1 and TSC2. Somatic mosaicism, as well as the size and complexity of the TSC1 and TSC2 loci, makes variant identification challenging. Indeed, in some individuals with a clinical diagnosis of TSC, diagnostic testing fails to identify an inactivating variant. To improve TSC1 and TSC2 variant detection, we screened the TSC1 and TSC2 genomic regions using targeted HaloPlex custom capture and next-generation sequencing (NGS) in genomic DNA isolated from peripheral blood of individuals with definite, possible or suspected TSC in whom no disease-associated variant had been identified by previous …

Less Is More? First Impressions From Cosmic-313, Pavlos Msaouel

Faculty, Staff and Student Publications

The COSMIC-313 phase 3 randomized controlled trial tested the triplet combination of cabozantinib with nivolumab and ipilimumab in comparison with nivolumab plus ipilimumab control as fist-line systemic therapy in metastatic clear cell renal cell carcinoma. The first results presented at the 2022 European Society of Medical Oncology Congress are a milestone for the renal cell carcinoma field because they signal the advent of triplet combinations as potential treatment options for our patients. The present commentary highlights some considerations and potential next steps based on these first impressions.

Editorial: Interplay Between Epigenetic Modifiers And Transcription Factors In Driving Cancer Progression, Yongyong Yang, Annalisa Di Ruscio, Satoshi Inoue, Guocan Wang, Shuai Gao

Faculty, Staff and Student Publications

No abstract provided.

Mechanisms Of Resistance To Egfr-Targeted Therapies In Colorectal Cancer: More Than Just Genetics, Christine Parseghian, Madhulika Eluri, Scott Kopetz, Kanwal Raghav

Faculty, Staff and Student Publications

The development of acquired resistance to anti-EGFR therapies remains poorly understood, with most research to date exploring, and trying to overcome, various genomic mechanisms of resistance. However, recent work supports a model of resistance whereby transcriptomic mechanisms of resistance predominate in the presence of active cytotoxic chemotherapy combined with anti-EGFR therapy in the first-line setting, with a greater predominance of acquired MAPK mutations after single-agent anti-EGFR therapy in the later-line setting. The proposed model has implications for prospective studies evaluating anti-EGFR rechallenge strategies guided by acquired MAPK mutations and highlights the need to address transcriptional mechanisms of resistance.

Retinal Alpha-Synuclein Accumulation Correlates With Retinal Dysfunction And Structural Thinning In The A53t Mouse Model Of Parkinson’S Disease, Katie K N Tran, Vickie H Y Wong, Anh Hoang, David I Finkelstein, Bang V Bui, Christine T O Nguyen

Faculty, Staff and Student Publications

Abnormal alpha-synuclein (α-SYN) protein deposition has long been recognized as one of the pathological hallmarks of Parkinson's disease's (PD). This study considers the potential utility of PD retinal biomarkers by investigating retinal changes in a well characterized PD model of α-SYN overexpression and how these correspond to the presence of retinal α-SYN. Transgenic A53T homozygous (HOM) mice overexpressing human α-SYN and wildtype (WT) control littermates were assessed at 4, 6, and 14  months of age (male and female,

Quality Care Is Equitable Care: A Call To Action To Link Quality To Achieving Health Equity Within Acute Care Surgery, Lisa M Knowlton, Tanya Zakrison, Lillian S Kao, Marta L Mccrum, Suresh Agarwal, Brandon Bruns, Kathie-Ann Joseph, Cherisse Berry

Faculty, Staff and Student Publications

Health equity is defined as the sixth domain of healthcare quality. Understanding health disparities in acute care surgery (defined as trauma surgery, emergency general surgery and surgical critical care) is key to identifying targets that will improve outcomes and ensure delivery of high-quality care within healthcare organizations. Implementing a health equity framework within institutions such that local acute care surgeons can ensure equity is a component of quality is imperative. Recognizing this need, the AAST (American Association for the Surgery of Trauma) Diversity, Equity and Inclusion Committee convened an expert panel entitled 'Quality Care is Equitable Care' at the 81st …

Unsheltered Homeless And Unstably Housed Adults Have Higher Levels Of Stress And More Health Risk Factors Than Sheltered Homeless Adults, Chaelin K Ra, Emily T Hébert, Adam Alexander, Darla E Kendzor, Robert Suchting, Michael S Businelle

Faculty, Staff and Student Publications

In the United States, approximately 580,000 individuals were homeless on a single night in 2020. Homelessness can be categorized into three subgroups: sheltered homeless, unsheltered homeless, and unstably housed. Few studies have examined the relations between homelessness subtypes, shelter service utilization, levels of stress experienced, and health risk factors. This study aimed to empirically examine whether shelter status the previous night was related to current stress, recent utilization of shelter-based mental health services, and current health risk factors. Data were collected at multiple homeless shelters in 2016 in the Oklahoma City area (N=575). All participants completed assessments of demographic characteristics, …

Resveratrol Rescues Cutaneous Radiation-Induced Dna Damage Via A Novel Ampk/Sirt7/Hmgb1 Regulatory Axis, Yi Jin, Xingyuan Liu, Xiaoting Liang, Jiabin Liu, Jieyu Liu, Zonglin Han, Qianxin Lu, Ke Wang, Bingyao Meng, Chunting Zhang, Minna Xu, Jian Guan, Li Ma, Liang Zhou

Faculty, Staff and Student Publications

Cutaneous radiation injury (CRI) interrupts the scheduled process of radiotherapy and even compromises the life quality of patients. However, the current clinical options for alleviating CRI are relatively limited. Resveratrol (RSV) has been shown to be a promising protective agent against CRI; yet the mechanisms of RSV enhancing radioresistance were not fully elucidated and limited its clinical application. In this study, we demonstrate RSV promotes cutaneous radioresistance mainly through SIRT7. During ionizing radiation (IR) treatment, RSV indirectly phosphorylates and activates SIRT7 through AMPK, which is critical for maintaining the genome stability of keratinocytes. Immunoprecipitation and mass spectrometry identified HMGB1 to …

Assessing The Most Vulnerable Subgroup To Type Ii Diabetes Associated With Statin Usage: Evidence From Electronic Health Record Data, Xinzhou Guo, Waverly Wei, Molei Liu, Tianxi Cai, Chong Wu, Jingshen Wang

Faculty, Staff and Student Publications

There have been increased concerns that the use of statins, one of the most commonly prescribed drugs for treating coronary artery disease, is potentially associated with the increased risk of new-onset Type II diabetes (T2D). Nevertheless, to date, there is no robust evidence supporting as to whether and what kind of populations are indeed vulnerable for developing T2D after taking statins. In this case study, leveraging the biobank and electronic health record data in the Partner Health System, we introduce a new data analysis pipeline and a novel statistical methodology that address existing limitations by (i) designing a rigorous causal …

Self-Assembling Peptides As Immunomodulatory Biomaterials, Andrea Hernandez, Jeffrey D Hartgerink, Simon Young

Faculty, Staff and Student Publications

Self-assembling peptides are a type of biomaterial rapidly emerging in the fields of biomedicine and material sciences due to their promise in biocompatibility and effectiveness at controlled release. These self-assembling peptides can form diverse nanostructures in response to molecular interactions, making them versatile materials. Once assembled, the peptides can mimic biological functions and provide a combinatorial delivery of therapeutics such as cytokines and drugs. These self-assembling peptides are showing success in biomedical settings yet face unique challenges that must be addressed to be widely applied in the clinic. Herein, we describe self-assembling peptides' characteristics and current applications in immunomodulatory therapeutics.

Il-8 Produced Via Bidirectional Communication Between Prostate Cancer And M2 Macrophages As A Potential Diagnostic And Prognostic Biomarker, Huihui Fan, Zheng Tang, Yaling Tian, Qingsong Lv, Fangyin Zeng

Faculty, Staff and Student Publications

PURPOSE: Owing to the mortality associated with metastatic prostate cancer and the shortcomings of the current parameters in predicting the disease prognosis, we require the identification of viable biomarkers, which would help in the diagnosis and prognosis of the disease. We aimed to determine whether the interleukin-8 level in the tumor microenvironment could serve as a potential clinical diagnostic marker and prognostic factor for prostate cancer.

METHODS: The migration assay of prostate cancer cells was performed in an in vitro co-culture model. Cell lines PC3 and DU145 were divided into two groups and co-cultured with M0 and M2 macrophages, respectively. …

Analysis Of Immune Intratumor Heterogeneity Highlights Immunoregulatory And Coinhibitory Lymphocytes As Hallmarks Of Recurrence In Stage I Non-Small Cell Lung Cancer, Alejandro Francisco-Cruz, Pedro Rocha, Alexandre Reuben, Santhoshi N Krishnan, Priyam Das, Runzhe Chen, Kelly Quek, Jun Li, Edwin R Parra, Luisa M Solis, Souptik Barua, Mei Jiang, Rossana Lazcano, Chi-Wan Chow, Carmen Behrens, Curtis Gumb, Latasha Little, Junya Fukuoka, Neda Kalhor, Annikka Weissferdt, Humam Kadara, John V Heymach, Stephen Swisher, Boris Sepesi, Arvind Rao, Cesar Moran, Jianhua Zhang, J Jack Lee, Junya Fujimoto, P Andrew Futreal, Ignacio I Wistuba, Christine B Peterson, Jianjun Zhang

Faculty, Staff and Student Publications

Our understanding of the molecular mechanisms underlying postsurgical recurrence of non-small cell lung cancer (NSCLC) is rudimentary. Molecular and T cell repertoire intratumor heterogeneity (ITH) have been reported to be associated with postsurgical relapse; however, how ITH at the cellular level impacts survival is largely unknown. Here we report the analysis of 2880 multispectral images representing 14.2% to 27% of tumor areas from 33 patients with stage I NSCLC, including 17 cases (relapsed within 3 years after surgery) and 16 controls (without recurrence ≥5 years after surgery) using multiplex immunofluorescence. Spatial analysis was conducted to quantify the minimum distance between …