Immunity Commons^™

From Antigen Presentation To Tumor Control: Mechanisms Of Type I Conventional Dendritic Cell-Based Cancer Vaccines, Josue E. Pineda

Dissertations and Theses (Open Access)

Type 1 conventional dendritic cells (cDC1s) are important for generating and sustaining antitumor immunity. Accordingly, the abundance of cDC1s in human tumors correlates with improved outcomes in cancer. Capitalizing on this role, we previously demonstrated that vaccination with in vitro-derived murine cDC1s elicits durable tumor control in multiple preclinical models; however, the immunological mechanisms underlying the efficacy of cDC1 vaccination remain unclear. Here, we examined whether in vitro-derived cDC1s resemble tumor-infiltrating DC populations and whether MHC-I and MHC-II antigen presentation contribute to cDC1-mediated tumor control following vaccination in melanoma.

As expected, MHC-I- or MHC-II-deficiency had minimal impact on …

Host-Intrinsic Factors Determine Anti-Tumor Efficacy Of Exercise In Pancreatic Ductal Adenocarcinoma, Sumedha Pareek

Dissertations and Theses (Open Access)

Pancreatic Ductal Adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths with a low 5-year relative survival rate of approximately 13.3% for all stages combined. We have previously shown that exercise can improve quality of life and enhance functional capacity among patients with PDAC. Exercise induces a variety of changes in the tumor microenvironment with beneficial effects in several tumor types. However, our understanding of the clinical effects of exercise and the mechanisms that mediate anti-tumor effects are limited in pancreatic cancer.

In this project, using C57BL/6 mice from Taconic Biosciences (Tac) and Jackson Laboratories (Jax), we established a …

Computational Frameworks To Unravel The Immune Landscape, Shan He

Dissertations and Theses (Open Access)

Recent advances in immunotherapy, including immune checkpoint blockade (ICB) and adoptive cell therapy, face challenges such as resistance and immune-related adverse events, partly due to our limited understanding of the immune signaling pathways. While high- throughput genomic data provide unprecedented resolution into these immune pathways, their full potential is limited by the lack of well-annotated, context-specific immune gene sets. To address this need, I developed a workflow to construct immune gene sets by integrating RNA- seq datasets and performing decomposition. Using this approach, I constructed 28 immune- specific gene sets from 83 bulk RNA-seq datasets and 12 Natural Killer (NK) …

Studies Of The Mechanisms Of Reverse Signaling By Cd40l, Barbara M. Nassif Rausseo

Dissertations and Theses (Open Access)

CD40 ligand (CD40L) is a transmembrane protein expressed on activated CD4 T cells, traditionally known for its role in forward signaling by engaging CD40 on antigen- presenting cells to promote immune activation. While this pathway is well characterized, there is evidence that CD40L also mediates reverse signaling, acting as a signaling receptor on T cells which enhances T cell function. However, the extent, consequences, and mechanism of CD40L-mediated reverse signaling in CD4 T cells remain poorly defined. This dissertation investigates the mechanisms and effects of CD40L reverse signaling on T cell function using both primary human T cells and the …

Expanding Inducible Epithelial Resistance Against Pneumonia: Novel Virus, Novel Receptor, Michael Longmire

Dissertations and Theses (Open Access)

Pneumonia is the leading infectious cause of death worldwide and presents a continuing risk among immunocompromised patients. Our work has been focused for many years on the phenomenon of inducible epithelial resistance, where activation of the innate immune response in the airway epithelium is necessary and sufficient to produce a pathogen-killing but self-protective environment to prevent severe disease. Inducible resistance is pathogen-agnostic and has been demonstrated against an array of respiratory infections. We achieve this using a combination of pattern recognition receptor agonists – Pam2CSK4 and ODN M362 being the current formulation – which produce synergistic levels of pathogen reduction …

Exploring Veto Activity: Dnam-1-Cd155 Axis In Overcoming Nk Cell-Mediated Allo-Rejection And Applications For Car-T Cell Therapy, Wei-Hsin Liu

Dissertations and Theses (Open Access)

As Miller et al. defined veto activity, it enables cells to target host cytotoxic T lymphocyte (CTL) precursors specific to veto cells' antigens, selectively eliminating anti- donor T cell clones without inducing rejection. By leveraging this unique immune property, two key research aims were proposed: “Exploration of the Impact of Veto Activity on Natural Killer (NK) Cell-Mediated Allo-rejection” and “Development of Off-the- shelf Chimeric Antigen Receptor (CAR)-T Therapy: Engineering Anti-Viral Veto CD8+ T Cells”. As demonstrated in our previous research, in a murine model with mild conditioning, anti-third-party central memory CD8+ veto T cells (veto Tcm) can prevent T cell- …

Mhc Class I Tyrosine Phosphorylation Site Y320 Augments Cd8+ T Cell Priming, Effector Function, And Memory Response, Yimo Sun, Gregory A Lizee, Yitao Tang, Priscilla Ortiz, R Eric Davis

Dissertations and Theses (Open Access)

The cytoplasmic domain of MHC class I (MHC-I) molecules contains a single, highly conserved tyrosine residue (Y320). In previous work, we found that mice expressing a Y320F-mutated form of H-2K^b had reduced capacity to generate K^b-restricted cytotoxic T lymphocyte (CTL) responses following viral infection, due (at least in part) to defects in endolysosomal trafficking of H-2K^b and antigen cross-presentation by dendritic cells (DCs). In this study, we investigated whether there are additional, post-presentation dependencies on Y320 for T-cell priming. We engineered both human- and mouse-derived antigen-presenting cells (APCs) to express either wild-type MHC-I or variants of …

Timigp: A Computational Framework To Determine The Tumor Immune Microenvironment Associated With Prognosis And Immunotherapy Response, Chenyang Li

Dissertations and Theses (Open Access)

Accumulating evidence has suggested that the tumor immune microenvironment (TIME) drastically impacts cancer patients’ clinical outcomes, including prognosis and immunotherapy response. However, understanding TIME remains challenging due to its complexity and heterogeneity. In this dissertation, we introduce TimiGP (Tumor Immune Microenvironment Illustration based on Gene Pairs), a computational framework designed to address this challenge. Leveraging single-cell RNA-seq (scRNA-seq) and bulk gene expression data alongside clinical information, TimiGP constructs a cell-cell interaction network that elucidates the relationship between immune cell function and relevant clinical outcomes, such as prognosis and treatment response. With immunological insights, these cell-cell interactions also facilitate the development …

The Role Of Lifr Signaling In Innate Immunity, Laura Kahn Serrudo

Dissertations and Theses (Open Access)

The localized signals that bone marrow (BM) hematopoietic stem cells (HSCs) and immune cells receive are critical in regulating their responses in the steady state and inflammation. Monocytes are an abundant and key population in the innate immune response that originates in the BM, and they circulate to monitor the periphery. Monocytes are composed of many subsets that have essential and specific functions, including swift egress from the BM, production of pro-inflammatory cytokines, and differentiation into monocyte-derived dendritic cells (MoDCs), which are required for efficient pathogen eradication.

Here, we uncovered LIFR (leukemia inhibitory factor receptor) restrains low-grade chronic inflammation in …

The Role Of Micrornas On Systemic And Central Nervous System- Inflammation In Aged Mice, Anik Banerjee

Dissertations and Theses (Open Access)

MicroRNAs play a crucial role in multiple biological processes, including development, cell differentiation, proliferation, metabolism, and cell death. Aberrant regulation of microRNAs is seen in many diseases, such as sepsis, cardiovascular disease, neurological diseases such as stroke, and metabolic disorders. Because of their involvement in disease processes, microRNAs have been investigated as both potential biomarkers, and as therapeutic targets. Age-related inflammatory diseases including diabetes, obesity, and atherosclerosis are important risk factors for infection and sepsis. Intestinal barrier impairment occurs with aging and after brain injuries, including stroke. Both aging and stroke increase the risk of infection and sepsis and are …

Mismatch Repair Deficient Neoantigen And Associated Circulating T-Cell Receptor Repertoires In Lynch Syndrome, Ana Bolivar

Dissertations and Theses (Open Access)

Lynch Syndrome (LS) is the most common inherited colorectal cancer (CRC) syndrome. It constitutes the perfect model to understand DNA mismatch repair deficient (MMRd) carcinogenesis, which underlies 15% of early-stage CRC. LS patients develop MMRd tumors with high loads of shared neoantigens (neoAgs), which are recognized by the immune system. Previous research has concentrated on discovering neoAgs and their potential as targets for vaccines in LS patients. However, these studies have primarily identified shared neoAgs from cancers, lacking detailed information on targetable neoAgs present in precancerous lesions. Understanding this landscape of pre-cancer derived neoAgs is crucial for intercepting cancer development …

Importance Of Specific Nk Cell Subsets For Antitumor Immunity In Hpv+ Cancers, Madison O'Hara

Dissertations and Theses (Open Access)

High-risk type human papillomaviruses (HPV) are associated with genital and oral cancers, and the incidence of HPV+ head and neck squamous cell cancers is fast increasing worldwide. Survival rates for patients with locally advanced disease are poor and variable after standard of care (SOC) treatment. Identifying the antitumor host immune mediators important for treatment response and designing strategies to promote them are essential for improving clinical outcome. The natural killer (NK) cells are a critical component for antitumor innate effector immunity. Among the multitude of activation and inhibitory receptors on immune cells, HLA-DR is recognized as an important activation marker …

Large-Scale Phenotyping Of Patients With Long Covid Post-Hospitalization Reveals Mechanistic Subtypes Of Disease, Felicity Liew, Claudia Efstathiou, Sara Fontanella, Matthew Richardson, Ruth Saunders, Dawid Swieboda, Jasmin K Sidhu, Stephanie Ascough, Shona C Moore, Noura Mohamed, Jose Nunag, Clara King, Olivia C Leavy, Omer Elneima, Hamish J C Mcauley, Aarti Shikotra, Amisha Singapuri, Marco Sereno, Victoria C Harris, Linzy Houchen-Wolloff, Neil J Greening, Nazir I Lone, Matthew Thorpe, A A Roger Thompson, Sarah L Rowland-Jones, Annemarie B Docherty, James D Chalmers, Ling-Pei Ho, Alexander Horsley, Betty Raman, Krisnah Poinasamy, Michael Marks, Onn Min Kon, Luke S Howard, Daniel G Wootton, Jennifer K Quint, Thushan I De Silva, Antonia Ho, Christopher Chiu, Ewen M Harrison, William Greenhalf, J Kenneth Baillie, Malcolm G Semple, Lance Turtle, Rachael A Evans, Louise V Wain, Christopher Brightling, Ryan S Thwaites, Peter J M Openshaw, Phosp-Covid Collaborative Group, Isaric Investigators

Faculty, Staff and Student Publications

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers …

Case Report: P40phox Deficiency Underlying Pediatric-Onset Systemic Lupus Erythematosus, Alejandro Nieto-Patlán, Natalia S Fernández Dávila, Yuqing Wang, Michelle Zelnick, Eyal Muscal, Martha Curry, James R Lupski, Steven M Holland, Bo Yuan, Douglas B Kuhns, Tiphanie P Vogel, Ivan K Chinn

Faculty, Staff and Students Publications

Introduction

Systemic lupus erythematosus is a multi-faceted autoimmune disorder of complex etiology. Pre-pubertal onset of pediatric systemic lupus erythematosus (pSLE) is uncommon and should raise suspicion for a genetic driver of disease. Autosomal recessive p40^phox deficiency is a rare immunologic disorder characterized by defective but not abolished NADPH oxidase activity with residual production of reactive oxygen species (ROS) by phagocytic cells.

Case presentation

We report the case of a now 18-year-old female with pSLE onset at 7 years of age. She presented with recurrent fever and malar rash. Aspects of her immune dysregulation over time have included typical pSLE …

Investigating The Distinct Role Of Pd-L2 In Modulating Human T Cells Responses, Anupallavi Srinivasamani

Dissertations and Theses (Open Access)

INVESTIGATING THE DISTINCT ROLE OF PD-L2 IN MODULATING HUMAN T CELL RESPONSES

Anupallavi Srinivasamani, M.S.

Advisory Professor: Michael A. Curran, Ph.D.

Therapeutic blockade of the Programmed cell death-1 (PD-1) receptor and its ligand Programmed death ligand-1 (PD-L1) has revolutionized the treatment of multiple cancers and made durable tumor regression a possibility in the clinic. PD-1 blockade prolonged progression-free survival and overall survival with lesser high-grade toxicity in patients with advanced melanoma when compared to the other FDA-approved checkpoint blockade target, CTLA-4. Unlike CTLA-4, PD-1 is unique in its ability to regulate T cell functions in lymphoid tissues as well as …

Molecular Mechanisms Behind Sars-Cov-2 Induced Host Genome Restructuring, Erin Simpson

Dissertations and Theses (Open Access)

Severe Acute Respiratory Syndrome Coronavirus -2 (SARS-CoV-2) has caused unprecedented morbidity and mortality worldwide. There are two pathophysiological hallmarks associated with severe patient outcomes after SARS-CoV-2 acute infection, namely delayed/weakened interferon production and overactive inflammatory responses. Our previous work has shown that these altered immune responses are due, at least in part, to significant alterations in 3D genome organization and epigenetic landscape following SARS-CoV-2 infection that are distinct from and more severe than changes caused by other viral infections or immune stimulants. While these changes at the chromatin level are important for understanding the immune dysregulation seen in some cases …

Role Of Il-17/Il-17ra Signaling In The Pancreatic Tumor Microenvironment, Susana Castro Pando, Susana Castro Pando

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second leading cause of cancer-related deaths. PDAC is characterized by the early establishment of a highly immunosuppressive fibro-cellular tumor microenvironment (TME). Our research has revealed the important role of IL-17 in the development and progression of pancreatic cancer, yet the specific cellular compartment responsible for IL-17-mediated tumor promotion remains unknown. We generated a transgenic mouse model with pancreatic KrasG12D activation and selective deletion of IL-17RA in the epithelial vs. immune component using either genetic manipulation or bone marrow transplantation. Deletion of IL17RA from the pancreatic epithelial compartment delayed premalignant lesion development …

Elucidating Mechanisms Involved In Host Microbial-Tumor Interactions, Vidhi Chandra

Dissertations and Theses (Open Access)

Cancer is a rising cause of mortality worldwide. Microbiota is the collection of micro-organisms that live inside our bodies and can impact the host health and disease by interacting with the immune and metabolic systems. The relationship between the microbiota and cancer is complex. Gut and intratumoral microbiota can affect cancer development and progression by influencing patient outcomes and therapy responsiveness in several cancer types. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer surrounded by a highly immuno-suppressive tumor microenvironment (TME) which limits efficacy of most available therapies. The tumoral niche provides a privileged microenvironment for microbial colonization that can …

Adipocytes And Innate Immunity In Systemic Sclerosis, Nancy Wareing

Dissertations and Theses (Open Access)

Systemic sclerosis (SSc; scleroderma) is a chronic systemic autoimmune and connective tissue disorder characterized by vasculopathy, autoimmune phenomena, and widespread fibrosis. Skin thickening and tightening is the cardinal feature of SSc and is responsible, in part, for the considerable morbidity of this disease. There are currently no targeted treatments for skin manifestations in SSc, primarily due to our fragmented understanding of its pathophysiologic mechanisms. In PART I, we report a previously unappreciated link between aberrant expression of the developmental gene sine oculis homeobox homolog 1 (SIX1) in skin-associated adipocytes in SSc skin and the early loss of dermal white adipose …

Doxorubicin-Induced Cardiotoxicity Is Mediated By Neutrophils Through Release Of Neutrophil Elastase, Anchit Bhagat

Dissertations and Theses (Open Access)

Doxorubicin (Dox) is one of the most effective chemotherapy agents that is used for the treatment of childhood cancer. Unfortunately Dox treatment can cause damage to the heart. Indeed, childhood cancer survivors are at a higher risk of developing a cardiovascular disease at an earlier age. The mechanisms by which Dox causes acute and late cardiotoxicity are not completely understood. One understudied area in Dox-induced cardiotoxicity is the contribution of inflammation and innate immune cells, in particular neutrophils. Recognizing that neutrophils have been implicated in a number of heart diseases, we evaluated the role of neutrophils in Dox-induced cardiotoxicity. Here, …

Effectiveness And Safety Of Immunosuppressants And Biological Therapy For Chronic Spontaneous Urticaria: A Network Meta-Analysis, Wen-Kuang Lin, Shwu-Jiuan Lin, Woan-Ruoh Lee, Chia-Chieh Lin, Weei-Chin Lin, Hua-Ching Chang, Chi-Tsun Cheng, Jason C Hsu

Faculty, Staff and Students Publications

Chronic spontaneous urticaria (CSU) is the most common phenotype of chronic urticaria. We compared treatment effects and safety profiles of the medications in patients with CSU. We searched PubMed, MEDLINE, and Web of Science for randomized control trials (RCTs), from 1 January 2000 to 31 July 2021, which evaluated omalizumab and immunosuppressants. Network meta-analyses (NMAs) were performed with a frequentist approach. Outcome assessments considered the efficacy (Dermatology Life Quality Index (DLQI) and weekly urticaria activity score (UAS7)) and tolerability profiles with evaluations of study quality, inconsistencies, and heterogeneity. We identified 14 studies which we included in our direct and indirect …

The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with dismal prognosis. The only curative option for patients is surgery, but over 80% of patients are not surgical candidates. Unfortunately, PDAC is resistant to the three remaining options. PDAC is characterized by a profoundly hypoxic and immunosuppressive stroma, which contributes to its therapeutic recalcitrance. Alpha-smooth muscle actin+ (αSMA+) cancer-associated fibroblasts (CAFs) are the most abundant stromal component, as well as mediators of stromal deposition. The hypoxia-inducible factors (HIF1 and HIF2) coordinate responses to hypoxia, yet, despite their known association to poor patient outcomes, their functions within the PDAC tumor microenvironment (TME) …

Atr-Mediated Cd47 And Pd-L1 Upregulation Restricts Radiotherapy-Induced Immune Priming And Abscopal Responses In Colorectal Cancer, Cheng-En Hsieh, Cheng-En Hsieh

Dissertations and Theses (Open Access)

Radiotherapy of colorectal cancer (CRC) can prime adaptive immunity against tumor-associated antigen (TAA)-expressing CRC cells systemically. However, incidences of abscopal tumor remission are extremely rare, and the post-irradiation immune escape mechanisms in CRC remain elusive. We report that CRC cells utilize a common DNA repair signaling pathway — ATR/Chk1/STAT3 — to upregulate both CD47 and PD-L1 in response to radiotherapy, which through engagement of SIRPα and PD-1 suppresses the capacity of antigen-presenting cells to phagocytose them thereby preventing TAA cross-presentation and innate immune activation. This post-irradiation CD47 and PD-L1 upregulation can be observed across various human solid tumor cells. Concordantly, …

Stat3 Inhibits Type I Interferon Signaling In Type I Conventional Dendritic Cells, Taylor Chrisikos

Dissertations and Theses (Open Access)

Conventional dendritic cells (cDCs) are an essential immune population, responsible for controlling adaptive immunity and tolerance. Recently, type I cDCs (cDC1s) have been delineated as a distinct cDC subset, uniquely responsible for coordinating T cell-mediated immunity against pathogens and tumors. Although the importance of cDC1s is now well established, the mechanisms that regulate cDC1 function remain largely unknown. Signal Transducer and Activator of Transcription 3 (STAT3) mediates the intracellular signaling of interleukin 10 (IL-10), an immunosuppressive cytokine. Therefore, we hypothesized that STAT3 and IL-10 inhibit cDC1 function and induction of T cell-mediated immunity. Herein, we show that IL-10 inhibits polyinosinic:polycytidylic …

Conserved Non-Pocket Interactions Drive The Diversity Of Peptide Presentation By Mhc Class I Molecules, Kyle Jackson

Dissertations and Theses (Open Access)

Cytotoxic T-lymphocytes (CTL) can lyse infected or transformed cells through recognition of peptides presented on human leukocyte antigen (HLA) molecules. A thorough understanding of peptide-HLA interactions is needed for improvement of CTL-based immunotherapies. We observed that aspartic acid (D) and glutamic acid (E) at peptide position 4 are highly prevalent in HLA-I peptide ligands, and discovered that they interact with arginine (R) in position 65 and lysine (L) in position 66 of the α1 helix of the binding groove in HLA-A*0201 and HLA-A*2402. Since this interaction differed from well-characterized peptide-HLA anchor interactions mediated by peptide position 2 and the C-terminus, …

Elucidating The Roles Of Il-15 In The Tumor Microenvironment, Rosa Maria Santana Carrero

Dissertations and Theses (Open Access)

ELUCIDATING THE ROLES OF IL-15 IN THE TUMOR MICROENVIRONMENT

Rosa M. Santana Carrero, B.S.

Advisory Professors: Shao-Cong Sun, Ph.D. & Kimberly S. Schluns, Ph.D.

Interleukin-15 (IL-15) is a factor that promotes activation, proliferation, cytotoxicity, and survival of CD8 T cells and NK cells, and has been shown to have anti-tumor effects. Moreover, loss of IL-15 expression in human colorectal tumors correlates with increased risk of relapse, diminished survival, decreased density and proliferation of T cells. All together these findings suggest that IL-15 expressed locally in the tumor microenvironment (TME) is an important mediator of anti-tumor responses by tumor infiltrating lymphocytes …

Micrornas Associated With Melanoma Inflammation And Response To Pd-1 Inhibition, Robert Szczepaniak Sloane

Dissertations and Theses (Open Access)

Melanoma is an aggressive malignancy of melanocytes with historically poor outcomes. Melanoma therapy has improved markedly over the past decade with advances in molecularly targeted agents and immunotherapies. Immune checkpoint inhibitors achieve T-cell mediated anti-tumor efficacy by blocking engagement of inhibitory checkpoints on T-cells to overcome immunosuppressive signals from tumor cells and the broader microenvironment. Despite these advances, there are a significant proportion of patients who do not benefit from existing immunotherapy strategies making it a priority to identify and target the mechanisms that confer resistance to therapy. We demonstrate that microRNAs are accurate markers of microenvironment composition with prognostic …

Fibroblast Heterogeneity In Pancreatic Cancer Immunity, Josephine Darpolor

Dissertations and Theses (Open Access)

Fibroblasts are a unique cell type defined by their mesenchymal phenotype and exclusion from epithelial, immune, and endothelial cell subsets. Although well studied in wound healing, cancer associated fibroblasts (CAFs) are incredibly heterogeneous, leading to contradictions as to the roles CAFs play in the tumor microenvironment (TME). CAFs were thought to be a barrier to treatment of pancreatic ductal adenocarcinoma (PDAC). However, general stromal targeting strategies have largely failed in the clinic likely due to the heterogeneity of CAFs in the TME. Therefore, our groups and others have worked to unravel the heterogeneity of CAFs in PDAC. In the works …

Investigating The Role Of Quaking In Antigen Uptake And Cross-Presentation By Dendritic Cells, Yating Li

Dissertations and Theses (Open Access)

Dendritic cells (DCs) are considered the most potent antigen presenting cells (APC) due to their superior capability of cross-presenting exogenous antigens to CD8⁺ T cell for strong adaptive immune responses. They internalize foreign antigens by phagocytosis, endocytosis or macropinocytosis, which are then processed in endosomal compartments and loaded onto MHC Class I molecules. However, the molecular mechanisms regulating exogenous antigen uptake and cross-presentation by DCs are not fully understood.

In this study, we discovered that an RNA-binding protein, Quaking (QKI) plays a pivotal role in antigen uptake by DCs. Our previous studies in neural stem cells and microglia have …

Exosomal Communication By Metastatic Osteosarcoma Cells Modulates Alveolar Macrophages To An M2 Tumor-Promoting Phenotype And Inhibits Tumoricidal Functions, Kerri Wolf

Dissertations and Theses (Open Access)

Osteosarcoma metastasizes to the lung, and there is a link between the predominance of tumor promoting immunosuppressive M2 macrophages in the metastases and poor patient survival. By contrast, M1macrophage predominance correlates with longer survival. M2 macrophages can be induced by various stimuli in the tumor microenvironment, including exosomes, which are 40- to 150-nm vesicles that are involved in intercellular communication and contribute to tumor progression and immune evasion. Recognizing that tumor cells can influence the tumor microenvironment to make it more permissive and because of the link between M2 dominance and curtailed patient survival, we evaluated the effect of …