Immunotherapy Commons^™

Ifnγ-Induced Antigen Loss In Chimeric Antigen Receptor-T Cell Therapy, Miao Cao, Jasmine Alvarez, Ramkrishna Mitra, Michael Xu, Trevor R. Baybutt, Zhengyang Sun, Oluwatobiloba Taylor, Allison Doermann, Ross E Staudt, Scott A. Waldman, Adam E. Snook

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

INTRODUCTION: FDA-approved chimeric antigen receptor (CAR)-expressing T cell therapies (CARTs) have revolutionized the treatment of blood cancers. Yet none have been successful for "solid" tumors, such as colorectal cancer (CRC), the 2nd leading cause of cancer deaths. Guanylyl cyclase C (GUCY2C) has emerged as a clinical-stage target for CART and bispecific T-cell engager (BiTE) therapies in CRC. IFNγ has been canonically recognized as beneficial for the effector functions of T cells by enhancing antigen processing and HLA presentation and is essential for CART targeting of solid malignancies by inducing adhesion molecule expression for synapse stabilization.

METHODS: Using

RESULTS: We identified …

Phase 1b/2 Study Of Bms-813160, A Ccr2/5 Dual Antagonist, In Combination With Chemotherapy Or Nivolumab In Patients With Advanced Pancreatic Or Colorectal Cancer, Dung T. Le, Gunnar Folprecht, Anna M. Varghese, Martin Gutierrez, Marcus Noel, Nikolaos A. Trikalinos, Eric Chen, Farshid Dayyani, S. Lindsey Davis, Wen Wee Ma, Atrayee Basu Mallick, Ignacio Garrido-Laguna, Mayu Osawa, Shaun O'Brien, Ruslan D. Novosiadly, Ke Xu, Danielle M. Greenawalt, Santanu Dutta, Christina Twyman Saint Victor, Heinz-Josef Lenz

Department of Medical Oncology Faculty Papers

BACKGROUND: Cysteine-cysteine chemokine receptors 2 (CCR2) and 5 (CCR5) contribute to immune suppression in tumor microenvironments. CCR2 and CCR5 antagonists have demonstrated antitumor activity in pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC), respectively. This phase 1b/2, open-label study evaluated BMS-813160, a CCR2/5 dual antagonist, in combination with chemotherapy±nivolumab in advanced PDAC or metastatic CRC.

METHODS: Part 1 included patients with metastatic untreated (first-line (1L)) PDAC, 1L CRC, or previously treated (second or third line (2/3L)) microsatellite stable (MSS) CRC. Patients received 2 weeks of BMS-813160 monotherapy (300 mg two times a day, 600 mg once daily, 300 mg once …

Baseline Lymphopenia Predicts Survival In Ici-Naïve Solid Tumor Patients Receiving Immune Checkpoint Inhibitors: A Propensity-Matched Real-World Pan-Cancer Analysis, Ahmed Ismail, Nina Balanchivadze, George R. Simon, Yanis Boumber

Department of Medicine Faculty Publications

Background: Baseline lymphopenia is common among advanced solid tumors and may influence the efficacy/safety of immune checkpoint inhibitors (ICIs), but large real-world evidence is limited. We evaluated the association between baseline absolute lymphocyte count (ALC) and clinical outcomes in adults with solid tumors treated with ICIs in routine practice. Methods: We performed a retrospective cohort study using TriNetX. Adults with solid tumors who received pembrolizumab, nivolumab, or atezolizumab (ICI-Naïve) between January 2015 and June 2026 were included. Baseline ALC was measured within 30 days before first treatment and was classified as lymphopenic (ALC < 1.5 × 10⁹/L) or non-lymphopenic (ALC ≥ 1.5 × 10⁹/L). Propensity score matching (1:1) yielded 5249 patients per group. The index date was the first immunotherapy date, and outcomes were assessed at 6, 12, 24, 36 months, and 5 years. The primary outcome was 24-month overall survival (OS); secondary outcomes were OS at 6 and 12 months and 6-month risks of healthcare utilization, immune-related adverse events (irAEs), and serious infections; and exploratory outcomes included OS at 36 months and 5 years. All outcomes were analyzed using Kaplan–Meier analysis, Cox proportional hazards models, and risk ratios. Subgroup analysis included OS stratified by solid tumor subtypes and prior lines of therapy. Results: After matching, patients with baseline lymphopenia …

Ovarian Cancer Immunology And Immunotherapy: Editorial Note, Chris D. Platsoucas

Biological Sciences Faculty Publications

[Introduction] As the guest editor of the Special Issue on Ovarian Cancer Immunology Immunotherapy, I would like to include certain brief comments on the current state of the field and to introduce the Special Issue. Ovarian carcinoma and malignant melanoma are the first human tumors where immune responses, primarily restricted to autologous tumor cells, were first demonstrated. T-cell lines and clones developed in recombinant interleukin-2 (rIL-2) from tumor-infiltrating lymphocytes (TIL) from these tumors exhibited cytotoxicity and/or cytokine production, primarily restricted to autologous tumor cells. The T-cell receptor (TCR) and the CD3 differentiation antigen on effector T cells and HLA on …

Multimodal Reprogramming Of The Tumor Microenvironment By Mmr And Dual Checkpoint Blockade In Hepatocellular Carcinoma Models, Mulu Z. Tesfay, Aleksandra Cios, Khandoker Usran Ferdous, Randal S. Shelton, Bahaa Mustafa, Camila C. Simoes, Murat Gokden, Isabelle R. Miousse, Kimberly J. Krager, Marjan Boerma, Alicja Urbaniak, Anuradha Kunthur, Sri Obulareddy, Joshua M. Eichhorn, Steven R. Post, Jean Christopher Chamcheu, Omeed Moaven, Chiswili Y. Chabu, Dan G. Duda, Matteo Conti, Bruno Nardo, Rang Govindarajan, Martin E. Fernandez-Zapico, Lewis R. Roberts, Mitesh J. Borad, Martin J. Cannon, Alexei G. Basnakian, Bolni M. Nagalo

School of Graduate Studies Faculty Publications

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, thus, there is an urgent need to develop more effective therapeutic options for this dismal condition. Tumor-infiltrating lymphocytes (TILs) are associated with improved response to immune checkpoint blockade in HCC, but their low abundance in most cases limits their therapeutic efficacy. Here, we demonstrate, in mice, that low-dose intratumoral immunovirotherapy with the trivalent measles, mumps, and rubella vaccine (MMR) induces superior tumor-growth delay and extended host survival compared to individually administered vaccines for measles, mumps, or rubella viruses. Further, our results show that MMR therapy synergizes with PD-1 and …

Advancing Peptide-Based Vaccines Against Candida: A Comparative Perspective On Liposomal And Synthetic Formulations, Hong Xin

School of Graduate Studies Faculty Publications

The growing threat of multidrug-resistant fungal pathogens, especially Candida auris, has underscored the need for effective antifungal vaccines. This commentary highlights recent advances in peptide-based vaccination using the SNAP (Spontaneous Nanoliposome Antigen Presentation) platform, focusing on the FM-SNAP vaccine, a bivalent liposomal formulation targeting the surface-expressed peptides fructose bisphosphate aldolase (Fba) and methionine synthase (Met6). Compared to earlier constructs such as MP12, FM-SNAP achieves superior immunogenicity and long-lasting protection at lower antigen doses. It elicits balanced Th1/Th2 cytokine responses and demonstrates durable efficacy in both immunocompetent and complement-deficient mouse models. The platform's compatibility with clinically approved adjuvants (MPLA and QS-21), …

Histologic And Immune Characterization Of Cutaneous Immune-Related Adverse Events Induced By Immune Checkpoint Inhibitors, Omar Pacha, Anisha B Patel, Jonathan L Curry, Cara L Haymaker, Nejla Ozirmak Lermi, Dzifa Yawa Duose, Ken Chen, Joud Hajjar, Aung Naing

Faculty, Staff and Student Publications

Background: Although immune checkpoint inhibitors (ICIs) are efficacious, they often cause immune-related adverse events (irAEs), most commonly cutaneous irAEs (CirAEs). The mechanisms underlying CirAEs remain unclear.

Methods: Attempting to better understand their mechanisms and histology we conducted a prospective study of 15 patients with advanced cancers treated with ICIs who developed grade 2 or higher CirAEs. Clinical and histologic characterization of biopsy specimens of CirAEs was performed. Histologic analysis of patient biopsy specimens were subdivided by epidermal reaction patterns that included spongiotic, lichenoid, and interface dermatitis patterns. A targeted RNA expression assay was used to identify immune markers in CirAE …

Ppp2r1a Mutations Portend Improved Survival After Cancer Immunotherapy, Yibo Dai, Anne Knisely, Mitsutake Yano, Minghao Dang, Emily M Hinchcliff, Sanghoon Lee, Annalyn Welp, Manoj Chelvanambi, Matthew Lastrapes, Heng Liu, Zhe Yuan, Chen Wang, Hao Nie, Stephanie Jean, Luis J Montaner, Jiakai Hou, Ami Patel, Shrina Patel, Bryan Fellman, Ying Yuan, Baohua Sun, Renganayaki Krishna Pandurengan, Edwin Roger Parra Cuentas, Joseph Celestino, Yan Liu, Jinsong Liu, R Tyler Hillman, Shannon N Westin, Anil K Sood, Pamela T Soliman, Aaron Shafer, Larissa A Meyer, David M Gershenson, David Vining, Dhakshinamoorthy Ganeshan, Karen Lu, Jennifer A Wargo, Weiyi Peng, Rugang Zhang, Linghua Wang, Amir A Jazaeri

Faculty, Staff and Student Publications

Immune checkpoint blockade (ICB) therapy is effective against many cancers, although resistance remains a major issue and new strategies are needed to improve clinical outcomes1-5. Here we studied ICB response in a cohort of patients with ovarian clear cell carcinoma-a cancer type that poses considerable clinical challenges and lacks effective therapies6-8. We observed significantly prolonged overall survival and progression-free survival in patients with tumours with PPP2R1A mutations. Importantly, our findings were validated in additional ICB-treated patient cohorts across multiple cancer types. Translational analyses from tumour biopsies demonstrated enhanced IFNγ signalling, and the presence of tertiary lymphoid structures at the baseline, …

Feasibility Of Manufacturing And Antitumor Activity Of Til For Advanced Endometrial Cancers, Yongliang Zhang, Kathleen N Moore, Amir A Jazaeri, Judy Fang, Ilabahen Patel, Andrew Yuhas, Patrick Innamarato, Nathan Gilbert, Joseph W Dean, Behzad Damirchi, Joe Yglesias, Rongsu Qi, Michelle R Simpson-Abelson, Erwin Cammaart, Sean R R Hall, Hequn Yin

Faculty, Staff and Student Publications

Lifileucel, a tumor-infiltrating lymphocyte (TIL) cell therapy approved for advanced melanoma, demonstrates promise for treating other solid tumors, including endometrial cancer (EC). The current study evaluates the feasibility of manufacturing TILs from EC tumors using Iovance’s proprietary 22-day Gen2 manufacturing process. Key parameters, including TIL yield, viability, immune phenotype, T-cell receptor clonality, and cytotoxic activity, were assessed. Of the 11 EC tumor samples processed at research scale, 10 (91%) successfully generated >1 × 109 viable TIL cells, with a median yield of 1.1 × 1010 cells and a median viability of 82.8%. Of the four EC tumor samples processed at …

Alfred Russel Wallace Notes 37. What About Wallace On Vaccination . . . ?, Charles H. Smith

Faculty/Staff Personal Papers

Best known for his natural history studies on evolution and biogeography, Alfred Russel Wallace (1823−1913) had a significant second career as a social critic. One of his most controversial stances was his position on (smallpox) vaccination. Anti-vaxxers of the present frequently bring up his name as a resource for their side, but the situation is not so easily reducible to that.

Mutation Of Smarca4 Induces Cancer Cell-Intrinsic Defects In The Enhancer Landscape And Resistance To Immunotherapy, Yawen Wang, Ismail M Meraz, Md Qudratullah, Sasikumar Kotagiri, Yanyan Han, Yuanxin Xi, Jing Wang, Kadir C Akdemir, Jack A Roth, Yonathan Lissanu

Faculty, Staff and Student Publications

Cancer genomic studies have identified frequent alterations in genes encoding components of the SWI/SNF chromatin remodeling complex, including SMARCA4 and ARID1A. Importantly, clinical reports indicate that SMARCA4-mutant lung cancers respond poorly to immunotherapy and have dismal prognosis. In this study, we corroborated the clinical findings by using immune-humanized, syngeneic, and genetically engineered mouse models of lung cancer harboring SMARCA4 deficiency. Specifically, models with SMARCA4 loss showed decreased response to anti-PD-1 immunotherapy associated with significantly reduced infiltration of dendritic cells and CD4+ T cells into the tumor microenvironment. SMARCA4 loss in tumor cells led to profound downregulation of STING1, IL1β, and …

Pd-L1 Testing, Treatment Patterns, And Clinical Outcomes Among Patients With Metastatic Nsclc At An Academic Medical Center, 2017-2021, Mehmet Altan, Dawen Sui, Cai Xu, George R Simon, Saliha T Sulihem, Donna Malveaux, Darcy Ponce, Waree Rinsurongkawong, Vadeerat Rinsurongkawong, J Jack Lee, Jianjun Zhang, Don L Gibbons, Ara A Vaporciyan, John V Heymach, Melissa L Santorelli, Thomas Burke, Loretta A Williams

Faculty, Staff and Student Publications

Introduction: Targeted therapies and immune checkpoint inhibitors (ICIs) have revolutionized the management of metastatic non-small cell lung cancer (NSCLC) over the past decade.

Methods: This single-center observational study was conducted to describe programmed death-ligand 1 (PD-L1) testing, choice of therapy, and outcomes for adult patients with stage IV NSCLC initiating first-line therapy from 2017 through 2020, with follow-up through June 2021. Patient characteristics and study assessments were described according to four histomolecular subtypes, defined by histologic characteristics and availability of standard-of-care therapies for molecular subgroups at the time of study conduct.

Results: Of 507 eligible patients with metastatic NSCLC, 85 …

Evolution Of The Tumor Immune Landscape During Treatment With Tebentafusp, A T Cell Receptor-Cd3 Bispecific, Joseph Sacco, Peter Kirk, Emma Leach, Alexander Shoushtari, Richard Carvajal, Camille Britton-Rivet, Sophie Khakoo, Laura Collins, Luis De La Cruz-Merino, Zeynep Eroglu, Alexandra Ikeguchi, Paul Nathan, Omid Hamid, Marcus Butler, Sarah Stanhope, Koustubh Ranade, Takami Sato

Department of Medical Oncology Faculty Papers

Metastatic uveal melanoma is an aggressive disease with poor outcome, which is refractory to immune checkpoint inhibitors. A T cell receptor (TCR)-based CD3 bispecific, tebentafusp, delivers clinical benefit in patients with metastatic uveal melanoma. Understanding the molecular basis for the anti-tumor activity of tebentafusp in an indication where checkpoint inhibitors are ineffective could aid in identification of other solid tumor indications where CD3 bispecifics may serve an unmet need. By analyzing tumor biopsies taken prior to treatment, early on-treatment, and at progression (NCT02570308), using RNA sequencing (RNA-seq) and immunohistochemistry (IHC), we show that expression of interferon-related genes in the tumor …

Modified Interferon-Gamma (Ifn-G) Receptors (Ifngr) To Enhance Cell-Based Immunotherapy, Eric Tran, Myungkyu Jang

Technology Transfer - Patents

No abstract provided.

Assessing Cancer Therapeutic Efficacy In Vivo Using [2h7]Glucose Deuterium Metabolic Imaging, Mario C Chang, Vinay R Malut, Rohit Mahar, Anna Rushin, Marc A Mcleod, Geraldine L Pierre, Indu R Malut, Stephen J Staklinski, Max E Glanz, Mukundan Ragavan, Gaurav Sharma, Manoj Madheswaran, Arshee Badar, Aparna D Rao, Brian K Law, Michael S Kilberg, James H P Collins, Vikram D Kodibagkar, James A Bankson, Ralph J Deberardinis, Matthew E Merritt

Faculty, Staff and Student Publications

Metabolic imaging produces powerful visual assessments of organ function in vivo. Current techniques can be improved by safely increasing metabolic contrast. The gold standard, 2-[18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging, is limited by radioactive exposure and sparse assessment of metabolism beyond glucose uptake and retention. Deuterium magnetic resonance imaging (DMRI) with [6,6-2H2]glucose is nonradioactive, achieves tumor metabolic contrast, but can be improved by enriched contrast from deuterated water (HDO) based imaging. Here, we developed a DMRI protocol employing [2H7]glucose. Imaging 2H-signal and measuring HDO production in tumor-bearing mice detected differential glucose utilization across baseline tumors, tumors treated with vehicle control or …

Chimeric Cd40 Polypeptides And Methods Of Use In Immunotherapy, Eric Tran, Myungkyu Jang, Timothy A Erickson

Technology Transfer - Patents

No abstract provided.

Immunological Biomarkers Of Response And Resistance To Treatment With Cabozantinib And Nivolumab In Recurrent Endometrial Cancer, Vladimir Roudko, Diane Marie Del Valle, Emir Radkevich, Geoffrey Kelly, Xie Hui, Manishkumar Patel, Edgar Gonzalez-Kozlova, Kevin Tuballes, Howard Streicher, Swati Atale, Lisa Wang, Benito Czinczin, Seunghee Kim-Schulze, Ignacio I Wistuba, Cara L Haymaker, Gheath Al-Atrash, Ganiraju Manyam, Jianjun Zhang, Ryan Thompson, Mayte Suarez-Farinas, Stephanie Lheureux, Sacha Gnjatic

Faculty, Staff and Student Publications

Background: Antiangiogenics combined with immune checkpoint blockade have become standard of care for recurrent endometrial cancer after standard platinum-based chemotherapy. To dissect mechanisms and define biomarkers associated with clinical outcomes to these combinations, we applied multidimensional immune monitoring to peripheral blood specimens collected from a randomized phase 2 trial of nivolumab with or without cabozantinib in 75 evaluable patients with recurrent endometrial cancer (NCI ETCTN 10104, NCT03367741). This trial demonstrated superiority of the combination to nivolumab alone.

Methods and results: Using Olink proteomics, mass cytometry, tumor antigen-specific ELISA, and whole exome tumor sequencing, we identified longitudinal immune signatures specific …

Inhibition Of Histone Methyltransferase Ezh2 For Immune Interception Of Colorectal Cancer In Lynch Syndrome, Charles M Bowen, Fahriye Duzagac, Abel Martel-Martel, Laura Reyes-Uribe, Mahira Zaheer, Jacklyn Thompson, Nan Deng, Ria Sinha, Soham Mazumdar, Melissa W Taggart, Abhinav K Jain, Elena Tosti, Winfried Edelmann, Krishna M Sinha, Eduardo Vilar

Faculty, Staff and Student Publications

Colorectal precancers in Lynch syndrome (LS) exhibit a distinct immune profile, presenting unique opportunities for developing immune-interception strategies to prevent carcinogenesis. Epigenetic modulation by EZH2 of immune-related genes is implicated in the carcinogenesis of different cancer types, including colorectal cancer. This study utilizes a mouse model of LS and ex vivo colonic organoids to assess the effects of the EZH2 inhibitor GSK503 on immune regulatory pathways, tumorigenesis, and epigenetic reprogramming. Our findings revealed that GSK503 significantly increased CD4+ and CD8+ T cells in both splenocytes and colonic mucosa of treated mice compared with controls. Additionally, a preventive dose of GSK503 …

Urine Proteomics Defines An Immune Checkpoint-Associated Nephritis Signature, James P Long, Shailbala Singh, Yanlan Dong, Cassian Yee, Jamie S Lin

Faculty, Staff and Student Publications

Immune checkpoint inhibitor (ICI) therapy is a cornerstone treatment for many cancers, but it can induce severe immunotoxicity, including acute interstitial nephritis (AIN). Currently, kidney biopsy is required to differentiate ICI-AIN from other causes of acute kidney injury (AKI). However, this invasive approach can lead to morbidity, delayed glucocorticoid treatment for patients with AIN, and unnecessarily prolonged suspension of ICI therapy in non-AIN patients. Delayed or incorrect diagnosis of ICI-AIN is particularly detrimental, as over 50% of patients are at risk of permanent renal damage. Thus, there is an urgent need for non-invasive biomarkers that can rapidly and accurately distinguish …

Targeted Inhibition Of Aurora Kinase A Promotes Immune Checkpoint Inhibition Efficacy In Human Papillomavirus-Driven Cancers, Soma Ghosh, Madison P O'Hara, Pragya Sinha, Tuhina Mazumdar, Lacin Yapindi, Jagannadha K Sastry, Faye M Johnson

Faculty, Staff and Student Publications

Background: Human papillomavirus (HPV)-driven cancers include head and neck squamous cell carcinoma and cervical cancer and represent approximately 5% of all cancer cases worldwide. Standard-of-care chemotherapy, radiotherapy, and immune checkpoint inhibitors (ICIs) are associated with adverse effects and limited responses in patients with HPV-driven cancers. The integration of targeted therapies with ICIs may improve outcomes. In a previous study, we demonstrated that Aurora kinase A (AURKA, Aurora A) inhibitors lead to apoptosis of human HPV-positive cancer cells in vitro and in vivo. Here, we explored the potential of Aurora A inhibition to enhance response to ICIs in immune-competent …

Recurrent And Metastatic Head And Neck Cancer: Mechanisms Of Treatment Failure, Treatment Paradigms, And New Horizons, William T. Barham, Marshall Patrick Stagg, Rula Mualla, Michael Dileo, Sagar Kansara

School of Medicine Faculty Publications

Background: Head and neck cancer is a deadly disease with over 500,000 cases annually worldwide. Metastatic head and neck cancer accounts for a large proportion of the mortality associated with this disease. Many advances have been made in our understanding of the mechanisms of metastasis. The application of immunotherapy to locally recurrent or metastatic head and neck cancer has not only improved oncologic outcomes but has also provided valuable insights into the mechanisms of immune evasion and ultimately treatment failure. Objectives: This review paper will review our current understanding of biological mechanisms of treatment failure and metastasis. Published and ongoing …

Early Treatment Discontinuation In Patients With Deficient Mismatch Repair Or Microsatellite Instability High Metastatic Colorectal Cancer Receiving Immune Checkpoint Inhibitors, Julien Taieb, Margherita Ambrosini, Emily Alouani, Sara Lonardi, Frank A Sinicrope, Marie Decraecker, Alice Boileve, Emilie Hafliger, Thibault Mazard, Simon Pernot, Pauline Parent, Javier Ros, Michael J Overman, Priya Jayachandran, Vincenzo Nasca, Lisa Salvatore, Rosine Guimbaud, Chiara Cremolini, David Tougeron, Filippo Pietrantonio

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitors (ICIs) are recommended to treat patients with deficient mismatch repair/microsatellite instability high (dMMR/MSI-H) metastatic colorectal cancer (mCRC). Pivotal trials have fixed a maximum ICI duration of 2 years, without a compelling rationale. A shorter treatment duration has the potential to improve patients' quality of life and reduce both toxicity and cost without compromising efficacy. Here we examine whether early treatment discontinuation (ETD) before 13 months in patients without progressive disease (PD) can lead to similar long-term disease control compared with a longer treatment duration (LTD).

Methods: To assess whether ETD is associated with similar outcomes compared …

Physical Ablative Methods And Cancer Cell Death: Implications For Immunity And Therapies, Alessandra Rossi, Claudia Muratori

Bioelectrics Publications

Surgery has traditionally been a cornerstone in cancer treatment, yet its feasibility can be limited by factors such as tumor location and patient health conditions. When surgery is not viable, thermal and pulsed electric field (PEF)-based ablation technologies offer valuable alternatives. Emerging evidence suggests that these approaches not only target tumors effectively but also stimulate antitumor immune responses. In this review, we begin by examining the distinctive features of hyperthermic treatments (radiofrequency and microwave ablation), cryoablation, and PEF-technologies. Subsequently, we discuss the mechanisms of cell death, stress responses, and release of danger signals triggered by these diverse ablation technologies. Finally, …

Depletion Of Adipose Stroma-Like Cancer-Associated Fibroblasts Potentiates Pancreatic Cancer Immunotherapy, Joseph Rupert, Alexes Daquinag, Yongmei Yu, Yulin Dai, Zhongming Zhao, Mikhail G Kolonin

Faculty, Staff and Student Publications

This study shows that populations of CAFs have distinct effects on pancreatic cancer progression and shows that depletion of CAFs expressing adipose markers potentiates tumor/metastasis suppression effects of immune checkpoint blockade.

Hsa-Mir-214-3p Inhibits Breast Cancer Cell Growth And Improves The Tumor Immune Microenvironment By Downregulating B7h3, Yan Lu, Kang Wang, Yuanhong Peng, Meng Chen, Lin Zhong, Luji Huang, F U Cheng, Xindan Sheng, Xin Yang, Manzhao Ouyang, George A Calin, Zhiwei He

Faculty, Staff and Student Publications

BACKGROUND: Immune checkpoint inhibitors play an important role in the treatment of solid tumors, but the currently used immune checkpoint inhibitors targeting programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T-lymphocyte antigen-4 (CTLA-4) show limited clinical efficacy in many breast cancers. B7H3 has been widely reported as an immunosuppressive molecule, but its immunological function in breast cancer patients remains unclear.

METHODS: We analyzed the expression of B7H3 in breast cancer samples using data from the Cancer Genome Atlas Program (TCGA) and the Gene Expression Omnibus (GEO) databases. MicroRNAs were selected using the TarBase, miRTarBase, and miRBase databases. …

Approved Car-T Therapies Have Reproducible Efficacy And Safety In Clinical Practice, Daniel Goyco Vera, Hiral Waghela, Mohamed Nuh, Jonathan Pan, Premal Lulla

Faculty, Staff and Students Publications

CAR-T cell therapy has established itself as a highly effective treatment for hematological malignancies. There are currently six commercial CAR-T products that have been FDA approved for diseases such as B-ALL, LBCL, MCL, FL, MM, and CLL/SLL. "Real-world" studies allow us to evaluate outcomes from the general population to determine their efficacy and safety compared to those who were included in the original trials. Based on several well conducted "Real-world" studies that represent diverse populations, we report that outcomes from the original trials that led to the approval of these therapies are comparable to those in practice.

Immune Checkpoint Inhibitor-Associated Cutaneous Adverse Events: Mechanisms Of Occurrence, Abdulaziz M. Eshaq, Thomas W. Flanagan, Abdulqader A. Ba Abbad, Zain Alabden A. Makarem, Mohammed S. Bokir, Ahmed K. Alasheq, Sara A. Al Asheikh, Abdullah M. Almashhor, Faroq Binyamani, Waleed A. Al-Amoudi, Abdulaziz S. Bawzir, Youssef Haikel, Mossad Megahed, Mohamed Hassan

School of Medicine Faculty Publications

Immunotherapy, particularly that based on blocking checkpoint proteins in many tumors, including melanoma, Merkel cell carcinoma, non-small cell lung cancer (NSCLC), triple-negative breast (TNB cancer), renal cancer, and gastrointestinal and endometrial neoplasms, is a therapeutic alternative to chemotherapy. Immune checkpoint inhibitor (ICI)-based therapies have the potential to target different pathways leading to the destruction of cancer cells. Although ICIs are an effective treatment strategy for patients with highly immune-infiltrated cancers, the development of different adverse effects including cutaneous adverse effects during and after the treatment with ICIs is common. ICI-associated cutaneous adverse effects include mostly inflammatory and bullous dermatoses, as …

Il-12 Encoding Ondv Synergizes With Car-T Cells In Orthotopic Models Of Non-Small Cell Lung Cancer, Amanda Rosewell Shaw, Daisuke Morita, Caroline E Porter, Eric Tu, Greyson W Biegert, Sonia Agrawal, Nicholas Durham, Malcolm K Brenner, Masataka Suzuki

Faculty, Staff and Students Publications

Systemic administration of oncolytic viruses (OVs) is a promising approach for targeting metastatic solid tumors, but their anti-tumor activity is limited by pre-existing neutralizing antibodies against common human viruses. Therefore, investigators have developed OVs derived from non-human host viruses. Successful implementation of this strategy requires that the viral vector selectively infects and replicates within human cancer cells. Newcastle disease virus (NDV) is an avian paramyxovirus that, as NDV-based OVs (oNDVs), has demonstrated safety and activity against multiple human tumors in clinical trials. Their use as a single agent, however, is insufficient to cure tumors. Similarly, chimeric antigen receptor-modified T cells …

Systematic Review Of Immune Checkpoint Inhibitor-Related Gastrointestinal, Hepatobiliary, And Pancreatic Adverse Events, Malek Shatila, Hao Chi Zhang, Anusha Shirwaikar Thomas, Antonio Pizuorno Machado, Sidra Naz, Nitish Mittal, Christine Catinis, Krishnavathana Varatharajalu, Carolina Colli Cruz, Eric Lu, Deanna Wu, Julie R Brahmer, Franck Carbonnel, Stephen B Hanauer, Bret Lashner, Bryan Schneider, John A Thompson, Michel Obeid, David P Farris, Yinghong Wang

Faculty, Staff and Student Publications

Gastrointestinal immune-related adverse events (GI irAEs) are common manifestations of immune checkpoint inhibitor (ICI) toxicity. We present a comprehensive systematic review of the incidence, management, and clinical course of irAEs across the entire GI system, including the luminal GI tract, liver, and pancreas. MEDLINE, Embase, Web of Science Core Collection, and Cochrane Library were used to conduct this review. All studies pertaining to GI irAEs were included. Both abstracts and full manuscripts were eligible if they included human subjects and were written in the English language. Articles not available in English, animal studies, or research not specific to GI toxicity …

Diaphragmatic Myopathy Associated With Dual Immune Checkpoint Inhibitors In A Patient With Renal Cell Carcinoma, Jeremy R Walder, Saadia A Faiz, Sudhakar Tummala, Shiao-Pei Weathers, Nicolas L Palaskas, Maryam Buni, Ajay Sheshadri, Lara Bashoura

Faculty, Staff and Student Publications

Immune-related adverse events (irAEs) have become increasingly prevalent with immune checkpoint inhibitor (ICI) cancer treatment. We present a 79-year-old man with metastatic renal cell carcinoma who developed shortness of breath and hypercapnic respiratory insufficiency after his first cycle of nivolumab and ipilimumab. Laboratory data showed elevated creatinine kinase, troponins, and transaminases. Computed tomography of the chest demonstrated bilateral lower lobe atelectasis. Heart catheterization and endomyocardial biopsy were unremarkable. Electromyogram (EMG) and nerve conduction studies (NCS) of the limb muscles revealed mild diffuse myopathy, normal sensory nerve conductions, and low-amplitude motor responses. Subsequent diaphragmatic EMG and NCS demonstrated severe myopathy. ICI-mediated …