Medical Specialties Commons^™

Clinical Characteristics And Cause Of Death Among Hospitalized Decedents With Cancer And Covid-19, Dereddi Raja Reddy, John A Cuenca, Joshua Botdorf, Mayoora Muthu, Ankit Hanmandlu, Robert Wegner, John Crommett, Cristina Gutierrez, Nisha Rathi, Bilja Sajith, Mark Knafl, Hussein A Abbas, Scott E Woodman, Joseph L Nates

Faculty, Staff and Student Publications

There is scant information on the clinical progression, end-of-life decisions, and cause of death of patients with cancer diagnosed with COVID-19. Therefore, we conducted a case series of patients admitted to a comprehensive cancer center who did not survive their hospitalization. To determine the cause of death, 3 board-certified intensivists reviewed the electronic medical records. Concordance regarding cause of death was calculated. Discrepancies were resolved through a joint case-by-case review and discussion among the 3 reviewers. During the study period, 551 patients with cancer and COVID-19 were admitted to a dedicated specialty unit; among them, 61 (11.6%) were nonsurvivors. Among …

A Phase I, Open-Label, Dose Confirmation, Escalation, And Expansion Trial Of Bi 1810631 As Monotherapy In Patients With Advanced Or Metastatic Solid Tumors With Her2 Aberrations, John Heymach, Frans Opdam, Minal Barve, Neil Gibson, Behbood Sadrolhefazi, Josep Serra, Noboru Yamamoto

Faculty, Staff and Student Publications

Background: BI 1810631 is a human HER2-selective tyrosine kinase inhibitor that covalently binds to both wild-type and mutated HER2 receptors, including exon 20 insertion mutations, whilst sparing EGFR signaling. This phase Ia/Ib, open-label, non-randomized study will determine the safety, maximum tolerated dose (MTD), pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of BI 1810631 in patients with HER2 aberration-positive solid tumors (NCT04886804).

Patients and methods: In phase Ia, patients with histologically/cytologically confirmed HER2 aberration-positive advanced/metastatic solid tumors will receive BI 1810631 orally twice daily (BID) or once daily (QD) at escalating doses. Starting dose level is 15 mg BID; QD …

Immune-Checkpoint Inhibitor Therapy Response Evaluation Using Oncophysics-Based Mathematical Models, Mustafa Syed, Matthew Cagely, Prashant Dogra, Lauren Hollmer, Joseph D Butner, Vittorio Cristini, Eugene J Koay

Faculty, Staff and Student Publications

The field of oncology has transformed with the advent of immunotherapies. The standard of care for multiple cancers now includes novel drugs that target key checkpoints that function to modulate immune responses, enabling the patient's immune system to elicit an effective anti-tumor response. While these immune-based approaches can have dramatic effects in terms of significantly reducing tumor burden and prolonging survival for patients, the therapeutic approach remains active only in a minority of patients and is often not durable. Multiple biological investigations have identified key markers that predict response to the most common form of immunotherapy-immune checkpoint inhibitors (ICI). These …

Impact Of High Neutrophil-To-Lymphocyte Ratio On Survival In Hospitalized Cancer Patients With Covid-19, Fernando A Díaz-Couselo, Santiago Flagel, Carla Nicolini, Sebastián Halac, Natalia Manzano, Marina Aguirre, Juan Rébora, Sandra Valle, Laura Noro, Chirayu Mohindroo, Florencia Mcallister, Marcelo Zylberman

Faculty, Staff and Student Publications

Neutrophil-to-lymphocyte ratio (NLR) has been studied as a prognostic factor for mortality in COVID-19 patients. Our study aimed to evaluate the association between NLR at COVID-19 diagnosis and survival during the following 90 days in hospitalized patients with solid cancer. Between May 2020 and June 2021, 120 patients were included in a retrospective cohort study. Univariable analysis showed patients with an NLR > 8.3 were associated with an increased risk of death (HR: 4.34; 95% CI: 1.74-10.84) compared to patients with NLR < 3.82 and with NLR ≥3.82 and ≤8.30 (HR: 2.89; 95% CI: 1.32-6.36). Furthermore, on multivariable analysis, NLR > 8.30 independently correlated with increased mortality. In patients with solid malignancies with COVID-19, an NLR > 8.3 is associated with …

On Target Methods To Induce Abscopal Phenomenon For Off-Target Effects: From Happenstance To Happenings, Blessie Elizabeth Nelson, Jacob J Adashek, Steven H Lin, Vivek Subbiah

Faculty, Staff and Student Publications

Although the "abscopal phenomenon" has been described several decades ago, this phenomenon lately has been obtaining momentous traction with the dawn of immune-based therapies. There has been increased cross talk among radiation oncologists, oncologists and immunologists and consequently a surge in the number of prospective clinical trials. This must be coupled with translation work from these clinical trials to aid in eventual identification of patients who may benefit. Abscopal effects may be induced by local and systemic methods, conventional radiotherapy, particle radiation, radionucleotide methods, cryoablation and brachytherapy. These approaches have all been reported to be stimulate abscopal effect. Immune induction …

Jaml Immunotherapy Targets Recently Activated Tumor-Infiltrating Cd8+ T Cells, Simon Eschweiler, Alice Wang, Ciro Ramírez-Suástegui, Adrian Von Witzleben, Yingcong Li, Serena J Chee, Hayley Simon, Monalisa Mondal, Matthew Ellis, Gareth J Thomas, Vivek Chandra, Christian H Ottensmeier, Pandurangan Vijayanand

Faculty, Staff and Student Publications

Junctional adhesion molecule-like protein (JAML) serves as a co-stimulatory molecule in γδ T cells. While it has recently been described as a cancer immunotherapy target in mice, its potential to cause toxicity, specific mode of action with regard to its cellular targets, and whether it can be targeted in humans remain unknown. Here, we show that JAML is induced by T cell receptor engagement, reveal that this induction is linked to cis-regulatory interactions between the CD3D and JAML gene loci. When compared with other immunotherapy targets plagued by low target specificity and end-organ toxicity, we find JAML to be mostly …

Recovering False Negatives In Crispr Fitness Screens With Jloe, Merve Dede, Traver Hart

Faculty, Staff and Student Publications

It is widely accepted that pooled library CRISPR knockout screens offer greater sensitivity and specificity than prior technologies in detecting genes whose disruption leads to fitness defects, a critical step in identifying candidate cancer targets. However, the assumption that CRISPR screens are saturating has been largely untested. Through integrated analysis of screen data in cancer cell lines generated by the Cancer Dependency Map, we show that a typical CRISPR screen has a ∼20% false negative rate, in addition to library-specific false negatives. Replicability falls sharply as gene expression decreases, while cancer subtype-specific genes within a tissue show distinct profiles compared …

Natural Killer T Cells And Other Innate-Like T Lymphocytes As Emerging Platforms For Allogeneic Cancer Cell Therapy, Amy N Courtney, Gengwen Tian, Leonid S Metelitsa

Faculty, Staff and Students Publications

T cells expressing chimeric antigen receptors (CARs) have achieved major clinical success in patients with hematologic malignancies. However, these treatments remain largely ineffective for solid cancers and require significant time and resources to be manufactured in an autologous setting. Developing alternative immune effector cells as cancer immunotherapy agents that can be employed in allogeneic settings is crucial for the advancement of cell therapy. Unlike T cells, Vα24-invariant natural killer T cells (NKTs) are not alloreactive and can therefore be generated from allogeneic donors for rapid infusion into numerous patients without the risk of graft-versus-host disease. Additionally, NKT cells demonstrate inherent …

Pan-Cancer Molecular Subtypes Of Metastasis Reveal Distinct And Evolving Transcriptional Programs, Yiqun Zhang, Fengju Chen, Chad J Creighton

Faculty, Staff and Students Publications

Molecular mechanisms underlying cancer metastasis span diverse tissues of origin. Here, we synthesize and collate the transcriptomes of patient-derived xenografts and patient tumor metastases, and these data collectively represent 38 studies and over 3,000 patients and 4,000 tumors. We identify four expression-based subtypes of metastasis transcending tumor lineage. The first subtype has extensive copy alterations, higher expression of MYC transcriptional targets and DNA repair genes, and bromodomain inhibitor response association. The second subtype has higher expression of genes involving metabolism and prostaglandin synthesis and regulation. The third subtype has evidence of neuronal differentiation, higher expression of DNA and histone methylation …

Waking Immune-Resistant Tumors With Neddylation, Kristin Huntoon, Wen Jiang, Betty Ys Kim

Faculty, Staff and Student Publications

The CD47/signal regulatory protein α (SIRPα) axis, which functions as an inhibitory phagocytosis checkpoint, also serves as a key mediator in cancer immune evasion. Many cancers, including colorectal cancer (CRC), exploit the expression of CD47 to escape phagocytic clearance and activate the innate immune system. Previous work has indicated that distinct paradigms of posttranslational modifications mediate the regulatory mechanisms of the CD47/SIRPα axis. In this issue of the JCI, Li et al. show that neddylation, a ubiquitin-like modification, inactivates Src homology region 2-containing protein tyrosine phosphatase 2 (SHP2), a downstream target of this pathway. They further show that inhibition of …

In Vivo Gene Delivery Into Mouse Mammary Epithelial Cells Through Mammary Intraductal Injection, Wen Bu, Yi Li

Faculty, Staff and Students Publications

Mouse mammary glands comprise ductal trees, which are lined by epithelial cells and have one opening at the tip of each nipple. The epithelial cells play a major role in mammary gland function and are the origin of most mammary tumors. Introducing genes of interest into mouse mammary epithelial cells is a critical step in evaluating gene function in epithelial cells and generating mouse mammary tumor models. This goal can be accomplished through the intraductal injection of a viral vector carrying the genes of interest into the mouse mammary ductal tree. The injected virus subsequently infects mammary epithelial cells, bringing …

Associations Of Financial Toxicity With Symptoms And Unplanned Healthcare Utilization Among Cancer Patients Taking Oral Chemotherapy At Home: A Prospective Observational Study, Yongfeng Chen, Zhenxiang Chen, Haiyun Jin, Yanrong Chen, Jinbing Bai, Guifen Fu

Faculty, Staff and Student Publications

Background: Cancer patients with financial toxicity experience psychological distress and often miss medical appointments and quit treatments early, which could be a barrier to the effective management of oral chemotherapy drugs at home. This study explores whether financial toxicity predicts symptoms and unplanned healthcare utilization among cancer patients taking oral chemotherapy at home, which will contribute to the safe management of oral chemotherapy.

Methods: Data in this study was from a prospective observational study, which was conducted between October 2018 and December 2019. 151 patients completed the Comprehensive Score for Financial Toxicity at discharge and completed the MD Anderson Symptom …

Factors For Poor Oral Health In Long-Term Childhood Cancer Survivors, Tushar Patni, Chun-Teh Lee, Yimei Li, Sue Kaste, Liang Zhu, Ryan Sun, Melissa M Hudson, Kirsten K Ness, Ana Neumann, Leslie L Robison

Faculty, Staff and Student Publications

Background: Survivors of childhood cancer are at risk for therapy-related dental diseases. The purpose of the study was to investigate the associations between clinical, socioeconomic, and demographic factors and oral diseases in the St. Jude Lifetime Cohort (SJLIFE) participants.

Methods: We performed a retrospective medical chart review and evaluated longitudinal self-reported dental outcomes in 4856 childhood cancer survivors and 591 community controls participating in the St. Jude Lifetime Cohort (SJLIFE) study. Univariate and multivariable logistic regression models were used to assess the impact of socioeconomic factors, treatment exposures and patient demographics on dental outcomes.

Results: Cancer survivors were more likely …

The Ra-Be-Real Multinational, Prospective, Observational Study In Patients With Rheumatoid Arthritis Receiving Baricitinib, Targeted Synthetic, Or Biologic Disease-Modifying Therapies: A 6-Month Interim Analysis, Rieke Alten, Gerd R Burmester, Marco Matucci-Cerinic, Jean-Hugues Salmon, Pedro Lopez-Romero, Walid Fakhouri, Inmaculada De La Torre, Liliana Zaremba-Pechmann, Thorsten Holzkämper, Bruno Fautrel

Faculty, Staff and Student Publications

INTRODUCTION: RA-BE-REAL has the overall aim of defining a profile of patients with rheumatoid arthritis (RA) starting baricitinib or any other targeted synthetic (ts) or any biologic (b) disease-modifying antirheumatic drug (DMARD) for the first time, and the primary objective of estimating time until discontinuation from any cause (excluding sustained response) of the initial treatment.

METHODS: RA-BE-REAL is an ongoing, prospective, observational, 36-month study in patients with RA initiating treatment with baricitinib (cohort A) or any other tsDMARD or any bDMARD (cohort B) for the first time. The primary objective is to assess the time until treatment discontinuation from any …

Spatiotemporal View Of Malignant Histogenesis And Macroevolution Via Formation Of Polyploid Giant Cancer Cells, Xiaoran Li, Yanping Zhong, Xudong Zhang, Anil K Sood, Jinsong Liu

Faculty, Staff and Student Publications

To understand how malignant tumors develop, we tracked cell membrane, nuclear membrane, spindle, and cell cycle dynamics in polyploid giant cancer cells (PGCCs) during the formation of high-grade serous carcinoma organoids using long-term time-lapse imaging. Single cells underwent traditional mitosis to generate tissue with uniform nuclear size, while others formed PGCCs via asymmetric mitosis, endoreplication, multipolar endomitosis, nuclear fusion, and karyokinesis without cytokinesis. PGCCs underwent restitution multipolar endomitosis, nuclear fragmentation, and micronuclei formation to increase nuclear contents and heterogeneity. At the cellular level, the development of PGCCs was associated with forming transient intracellular cells, termed fecundity cells. The fecundity cells …

International Multicenter Study Comparing Covid-19 In Patients With Cancer To Patients Without Cancer: Impact Of Risk Factors And Treatment Modalities On Survivorship., Issam I Raad, Ray Hachem, Nigo Masayuki, Tarcila Datoguia, Hiba Dagher, Ying Jiang, Vivek Subbiah, Bilal Siddiqui, Arnaud Bayle, Robert Somer, Ana Fernández Cruz, Edward Gorak, Arvinder Bhinder, Nobuyoshi Mori, Nelson Hamerschlak, Samuel Shelanski, Tomislav Dragovich, Yee Elise Vong Kiat, Suha Fakhreddine, Abi Hanna Pierre, Roy F Chemaly, Victor Mulanovich, Javier Adachi, Jovan Borjan, Fareed Khawaja, Bruno Granwehr, Teny John, Eduardo Yepez Yepez, Harrys A Torres, Natraj Reddy Ammakkanavar, Marcel Yibirin, Cielito C Reyes-Gibby, Mala Pande, Noman Ali, Raniv Dawey Rojo, Shahnoor M Ali, Rita E Deeba, Patrick Chaftari, Takahiro Matsuo, Kazuhiro Ishikawa, Ryo Hasegawa, Ramón Aguado-Noya, Alvaro Garcia García, Cristina Traseira Puchol, Dong Gun Lee, Monica Slavin, Benjamin Teh, Cesar A Arias, Dimitrios P Kontoyiannis, Alexandre E Malek, Anne-Marie Chaftari

Oncology Articles

BACKGROUND: In this international multicenter study, we aimed to determine the independent risk factors associated with increased 30 day mortality and the impact of cancer and novel treatment modalities in a large group of patients with and without cancer with COVID-19 from multiple countries.

METHODS: We retrospectively collected de-identified data on a cohort of patients with and without cancer diagnosed with COVID-19 between January and November 2020 from 16 international centers.

RESULTS: We analyzed 3966 COVID-19 confirmed patients, 1115 with cancer and 2851 without cancer patients. Patients with cancer were more likely to be pancytopenic and have a smoking history, …

Using Cognitive Interviews To Improve A Measure Of Organizational Readiness For Implementation, Maria Mcclam, Lauren Workman, Emanuelle M Dias, Timothy J Walker, Heather M Brandt, Derek W Craig, Robert Gibson, Andrea Lamont, Bryan J Weiner, Abraham Wandersman, Maria E Fernandez

Faculty, Staff and Student Publications

BACKGROUND: Organizational readiness is a key factor for successful implementation of evidence-based interventions (EBIs), but a valid and reliable measure to assess readiness across contexts and settings is needed. The R = MC

METHODS: We conducted 20 cognitive interviews with FQHC staff (clinical and non-clinical) in South Carolina and Texas. Participants were provided a subset of items from the readiness survey to review. A semi-structured interview guide was developed to elicit feedback from participants using "think aloud" and probing techniques. Participants were recruited using a purposive sampling approach and interviews were conducted virtually using Zoom and WebEx. Participants were asked …

Generation Of A Tree Shrew Breast Cancer Model Using Lentivirus Expressing Pik3ca-H1047r, Li Zeng, Hong-Yan Zhang, Chuan-Yu Yang, Zhuo Cheng, Qiu-Yun Jiang, Yao Luo, Yi Li, Fu-Bing Li, Ce-Shi Chen

Faculty, Staff and Students Publications

No abstract provided.

Diverticular Disease And Cancer Risk: More Than A Gut Feeling, Veronika Fedirko, Scott Kopetz, Carrie R Daniel

Faculty, Staff and Student Publications

No abstract provided.

Technology Meets Tils: Deciphering T Cell Function In The -Omics Era, William H Hudson, Andreas Wieland

Faculty, Staff and Students Publications

T cells are at the centerstage of cancer immunology due to their ability to recognize mutations within tumor cells and directly mediate cancer cell killing. Immunotherapies to rejuvenate exhausted T cell responses have transformed the clinical management of several malignancies. In parallel, the development of novel multidimensional analysis platforms such as single-cell RNA-sequencing and high-dimensional flow cytometry has yielded unprecedented insights into immune cell biology. This convergence has revealed substantial heterogeneity of tumor-infiltrating immune cells, both within single tumors, across tumor types, and among cancer patients. Here, we discuss the opportunities and challenges of studying the complex tumor microenvironment with …

Technology Meets Tils: Deciphering T Cell Function In The -Omics Era, William H Hudson, Andreas Wieland

Faculty, Staff and Students Publications

T cells are at the centerstage of cancer immunology due to their ability to recognize mutations within tumor cells and directly mediate cancer cell killing. Immunotherapies to rejuvenate exhausted T cell responses have transformed the clinical management of several malignancies. In parallel, the development of novel multidimensional analysis platforms such as single-cell RNA-sequencing and high-dimensional flow cytometry has yielded unprecedented insights into immune cell biology. This convergence has revealed substantial heterogeneity of tumor-infiltrating immune cells, both within single tumors, across tumor types, and among cancer patients. Here, we discuss the opportunities and challenges of studying the complex tumor microenvironment with …

Civicdb 2022: Evolution Of An Open-Access Cancer Variant Interpretation Knowledgebase, Kilannin Krysiak, Arpad M Danos, Jason Saliba, Joshua F Mcmichael, Adam C Coffman, Susanna Kiwala, Erica K Barnell, Lana Sheta, Cameron J Grisdale, Lynzey Kujan, Shahil Pema, Jake Lever, Sarah Ridd, Nicholas C Spies, Veronica Andric, Andreea Chiorean, Damian T Rieke, Kaitlin A Clark, Caralyn Reisle, Ajay C Venigalla, Mark Evans, Payal Jani, Hideaki Takahashi, Avila Suda, Peter Horak, Deborah I Ritter, Xin Zhou, Benjamin J Ainscough, Sean Delong, Chimene Kesserwan, Mario Lamping, Haolin Shen, Alex R Marr, My H Hoang, Kartik Singhal, Mariam Khanfar, Brian V Li, Wan-Hsin Lin, Panieh Terraf, Laura B Corson, Yasser Salama, Katie M Campbell, Kirsten M Farncombe, Jianling Ji, Xiaonan Zhao, Xinjie Xu, Rashmi Kanagal-Shamanna, Ian King, Kelsy C Cotto, Zachary L Skidmore, Jason R Walker, Jinghui Zhang, Aleksandar Milosavljevic, Ronak Y Patel, Rachel H Giles, Raymond H Kim, Lynn M Schriml, Elaine R Mardis, Steven J M Jones, Gordana Raca, Shruti Rao, Subha Madhavan, Alex H Wagner, Malachi Griffith, Obi L Griffith

Faculty, Staff and Students Publications

CIViC (Clinical Interpretation of Variants in Cancer; civicdb.org) is a crowd-sourced, public domain knowledgebase composed of literature-derived evidence characterizing the clinical utility of cancer variants. As clinical sequencing becomes more prevalent in cancer management, the need for cancer variant interpretation has grown beyond the capability of any single institution. CIViC contains peer-reviewed, published literature curated and expertly-moderated into structured data units (Evidence Items) that can be accessed globally and in real time, reducing barriers to clinical variant knowledge sharing. We have extended CIViC's functionality to support emergent variant interpretation guidelines, increase interoperability with other variant resources, and promote widespread dissemination …

Phase I Dose Escalation Study Of Topical Bexarotene In Women At High Risk For Breast Cancer, Parijatham S Thomas, Anisha B Patel, J Jack Lee, Diane D Liu, Mike Hernandez, Miguel Muzzio, Alejandro Contreras, Valerie Sepeda, Carrie Mays, Diane Weber, Lana A Vornik, Seema A Khan, Eileen Dimond, Brandy M Heckman-Stoddard, Marjorie Perloff, Powel H Brown

Faculty, Staff and Student Publications

Bexarotene is a rexinoid that has been shown to prevent mammary tumors in mouse models but oral dosing has toxicities. This phase I study evaluates topical bexarotene, as a potential chemoprevention agent, for safety and toxicity in high-risk women for breast cancer.

Molecular Mechanisms And Future Implications Of Vegf/Vegfr In Cancer Therapy, Sonia A Patel, Monique B Nilsson, Xiuning Le, Tina Cascone, Rakesh K Jain, John V Heymach

Faculty, Staff and Student Publications

Angiogenesis, the sprouting of new blood vessels from existing vessels, is one of six known mechanisms employed by solid tumors to recruit blood vessels necessary for their initiation, growth, and metastatic spread. The vascular network within the tumor facilitates the transport of nutrients, oxygen, and immune cells and is regulated by pro- and anti-angiogenic factors. Nearly four decades ago, VEGF was identified as a critical factor promoting vascular permeability and angiogenesis, followed by identification of VEGF family ligands and their receptors (VEGFR). Since then, over a dozen drugs targeting the VEGF/VEGFR pathway have been approved for approximately 20 solid tumor …

Obesity Is Associated With Altered Tumor Metabolism In Metastatic Melanoma, Andrew W Hahn, Ashley V Menk, Dayana B Rivadeneira, Ryan C Augustin, Mingchu Xu, Jun Li, Xiaogang Wu, Aditya K Mishra, Tuba N Gide, Camelia Quek, Yan Zang, Christine N Spencer, Alexander M Menzies, Carrie R Daniel, Courtney W Hudgens, Theodore Nowicki, Lauren E Haydu, M A Wadud Khan, Vancheswaran Gopalakrishnan, Elizabeth M Burton, Jared Malke, Julie M Simon, Chantale Bernatchez, Nagireddy Putluri, Scott E Woodman, Y N Vashisht Gopal, Renato Guerrieri, Grant M Fischer, Jian Wang, Khalida M Wani, John F Thompson, Jeffrey E Lee, Patrick Hwu, Nadim Ajami, Jeffrey E Gershenwald, Georgina V Long, Richard A Scolyer, Michael T Tetzlaff, Alexander J Lazar, Dirk Schadendorf, Jennifer A Wargo, John M Kirkwood, Ralph J Deberardinis, Han Liang, Andrew Futreal, Jianhua Zhang, James S Wilmott, Weiyi Peng, Michael A Davies, Greg M Delgoffe, Yana G Najjar, Jennifer L Mcquade

Faculty, Staff and Student Publications

PURPOSE: Overweight/obese (OW/OB) patients with metastatic melanoma unexpectedly have improved outcomes with immune checkpoint inhibitors (ICI) and BRAF-targeted therapies. The mechanism(s) underlying this association remain unclear, thus we assessed the integrated molecular, metabolic, and immune profile of tumors, as well as gut microbiome features, for associations with patient body mass index (BMI).

EXPERIMENTAL DESIGN: Associations between BMI [normal (NL < 25) or OW/OB (BMI ≥ 25)] and tumor or microbiome characteristics were examined in specimens from 782 patients with metastatic melanoma across 7 cohorts. DNA associations were evaluated in The Cancer Genome Atlas cohort. RNA sequencing from 4 cohorts (n = 357) was batch corrected and gene set enrichment analysis (GSEA) by BMI category was performed. Metabolic profiling was conducted in a subset of patients (x = 36) by LC/MS, and in flow-sorted melanoma tumor cells (x = 37) and patient-derived melanoma cell lines (x = 17) using the Seahorse XF assay. Gut microbiome features were examined in an independent cohort (n = 371).

RESULTS: DNA mutations and copy number variations were not associated with BMI. GSEA demonstrated that tumors from OW/OB patients were metabolically quiescent, with downregulation of oxidative phosphorylation and multiple other metabolic pathways. Direct metabolite analysis and functional metabolic profiling confirmed decreased …

Vista Targeting Of T-Cell Quiescence And Myeloid Suppression Overcomes Adaptive Resistance, Evelien Schaafsma, Walburga Croteau, Mohamed Eltanbouly, Elizabeth C Nowak, Nicole C Smits, Jie Deng, Aurelien Sarde, Cecilia A Webber, Dina Rabadi, Chao Cheng, Randolph Noelle, J Louise Lines

Faculty, Staff and Students Publications

VISTA is a premier target for cancer treatment due to its broad expression in many cancer types and enhanced expression upon development of adaptive immune checkpoint resistance. In the CT26 colorectal cancer model, monotherapy of small tumors with anti-VISTA resulted in slowed tumor growth. In a combination therapy setting, large CT26 tumors showed complete adaptive resistance to anti-PD-1/CTLA-4, but inclusion of anti-VISTA led to rejection of half the tumors. Mechanisms of enhanced anti-tumor immunity were investigated using scRNA-seq, multiplex image analysis and flow cytometry of the tumor immune infiltrate. In both treatment models, anti-VISTA upregulated stimulated antigen-presentation pathways and reduced …

Increased Camkk2 Expression Is An Adaptive Response That Maintains The Fitness Of Tumor-Infiltrating Natural Killer Cells, Patrick K Juras, Luigi Racioppi, Debarati Mukherjee, Sandeep Artham, Xia Gao, Laura Akullian D'Agostino, Ching-Yi Chang, Donald P Mcdonnell

Faculty, Staff and Students Publications

Calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a key regulator of energy homeostasis in several cell types. Expression of this enzyme in tumor cells promotes proliferation and migration, and expression in tumor-associated immune cells facilitates M2 macrophage polarization and the development of myeloid-derived suppressor cells. Thus, there has been interest in developing CaMKK2 inhibitors as potential anticancer therapeutics. One impediment to clinical development of these agents is that the roles of CaMKK2 in other cellular compartments within the tumor immune microenvironment remain to be established. We report herein that CaMKK2 is expressed at low basal levels in natural killer (NK) …

Giant Mesenchymal Hepatic Hamartomas With Adrenal Involvement Precipitating Respiratory Failure: A Myxomatous Mystery In A 3 Month Old, Ali Yasback, Abid Ulhaque, Tushar Chandra, Sandor Szilagyi

West Florida Division GME Research Day 2023

No abstract provided.

Aggressive Digital Papillary Adenocarcinoma, Jessica A. Thomas, Alexandra E. Thomson, Savannah Grunhard, George Negrea

South Atlantic Division GME Research Day 2023

No abstract provided.

Under The Skin: Unidentified Subcutaneous Nodules, Jacob Trimble, Sarah Puim

South Atlantic Division GME Research Day 2023

No abstract provided.