Targeting Immune Checkpoints in Esophageal Cancer: A High Mutational Load Tumor Rajeev Dhupar, MD, Lauren Van Der Kraak, PhD, Arjun Pennathur, MD, Matthew.

Slides:

Advertisements

Similar presentations

Interferons Induction of synthesis Induction of antiviral activity Antiviral activities induced by interferons  and  Antiviral activities induced by.

Advertisements

Targeting Immune Checkpoints in Esophageal Cancer: A High Mutational Load Tumor Rajeev Dhupar, MD, Lauren Van Der Kraak, PhD, Arjun Pennathur, MD, Matthew.

David P. Carbone, MD, PhD, David R. Gandara, MD, Scott J

Tumor Immunity: Exploring the Role of a Checkpoint

Figure 1 CTLA-4 and PD-1–PD-L1 immune checkpoints

Lung Adenocarcinoma and Squamous Cell Carcinoma Gene Expression Subtypes Demonstrate Significant Differences in Tumor Immune Landscape Hawazin Faruki,

Immunotherapy of hepatocellular carcinoma

Immunologic pathomechanism of Hodgkin's lymphoma

The yin and yang of evasion and immune activation in HCC

Tumor Immunology Ali Al Khader, MD Faculty of Medicine

Nat. Rev. Gastroenterol. Hepatol. doi: /nrgastro

Immune Prophets of Lung Cancer: The Prognostic and Predictive Landscape of Cellular and Molecular Immune Markers Ivana Catacchio, Anna Scattone, Nicola.

Figure 1 Immunomodulatory monoclonal antibodies and armoured chimeric antigen receptor (CAR) T cells overcome immune suppression Figure 1 | Immunomodulatory.

Figure 3 Altered adaptive immune functions after sepsis

Cancer Immunotherapy by Dendritic Cells

Antibody-modified T cells: CARs take the front seat for hematologic malignancies by Marcela V. Maus, Stephan A. Grupp, David L. Porter, and Carl H. June.

Oncology Meets Immunology: The Cancer-Immunity Cycle

Toll-like receptors: Applications to dermatologic disease

Immunologic pathomechanism of Hodgkin's lymphoma

Latest Advances in Chemotherapeutic, Targeted, and Immune Approaches in the Treatment of Metastatic Melanoma Darshil J. Shah, MD, MPH, Roxana S. Dronca,

Nat. Rev. Gastroenterol. Hepatol. doi: /nrgastro

Nat. Rev. Gastroenterol. Hepatol. doi: /nrgastro

Markers of cancer cell and lymphocytes in inflammatory infiltration around a tumour as potential markers of immunomodulatory treatment response. Markers.

Aaron M. Abarbanell, MD, Arthur C. Coffey, MD, John W

Megan E. Daly, MD, Arta M. Monjazeb, MD, PhD, Karen Kelly, MD

David P. Carbone, MD, PhD, David R. Gandara, MD, Scott J

Malaria Vaccine Design: Immunological Considerations

Colorectal cancer vaccines: Principles, results, and perspectives

Oncologic Outcomes After Surgical Resection of Subcentimeter Non-Small Cell Lung Cancer Matthew J. Schuchert, MD, Arman Kilic, BS, Arjun Pennathur, MD,

Lisa M. Brown, MD, MAS, David T. Cooke, MD, Elizabeth A. David, MD

Georges Makhoul, MD, MS, Ray C.J. Chiu, MD, PhD, Renzo Cecere, MD, MS

Incorporating Immune-Checkpoint Inhibitors into Systemic Therapy of NSCLC Stéphane Champiat, MD, Ecaterina Ileana, MD, Giuseppe Giaccone, MD, PhD, Benjamin.

How to Keep the Treatment of Esophageal Disease in the Surgeon’s Hands

Leonardo V. Riella, Mohamed H. Sayegh Kidney International Supplements

Moving Immune Checkpoint Blockade in Thoracic Tumors beyond NSCLC

Nat. Rev. Rheumatol. doi: /nrrheum

Figure 1 The role of CTLA4 and PD1 in T cell activation

Targets for immunotherapy of liver cancer

Takehito Shukuya, MD, PhD, David P. Carbone, MD, PhD

The yin and yang of evasion and immune activation in HCC

Robert J Korst, MD, Ronald G Crystal, MD

Mechanisms of immune escape in the tumor microenvironment.

Expression of Bone Morphogenetic Proteins in Human Lung Carcinomas

William T. Mahle, MD, Emilia Matthews, MS, Kirk R. Kanter, MD, Brian E

Nat. Rev. Endocrinol. doi: /nrendo

Johan Botling, MD, PhD, Martin Sandelin, MD, PhD

Volume 33, Issue 4, Pages (October 2010)

Valder R Arruda, Patricia Favaro, Jonathan D Finn Molecular Therapy

Brendon M. Stiles, MD, Mohamed K. Kamel, MD, Sebron W

Predictors of Long-Term Survival After Resection of Esophageal Carcinoma With Nonregional Nodal Metastases Paul C. Lee, MD, Jeffrey L. Port, MD, Subroto.

Nat. Rev. Urol. doi: /nrurol

Radiofrequency Ablation for the Treatment of Pulmonary Metastases

Completely Thrombosed Tricuspid Pouch Mimicking a Cardiac Tumor

Arman Kilic, BS, Matthew J. Schuchert, MD, Brian L

Figure 3 Underlying mechanisms of TREG cells in atherosclerosis

Tumor Immunology Ali Al Khader, MD Faculty of Medicine

Cell-mediated immunity Regulation of the immune response

Postesophagectomy Chylothorax: Incidence, Risk Factors, and Outcomes

Distribution of immune checkpoint in tumor cells and immune microenvironment. CTLA-4, cytotoxic T lymphocyte antigen-4; MHC, major histocompatibility complex;

Matthew J. Schuchert, MD, Omar Awais, DO, Ghulam Abbas, MD, Zachary D

Releasing the Brakes on Cancer Immunotherapy

Vaccines for Lung Cancer

Dendritic-Cell-Based Therapeutic Cancer Vaccines

Matthew J. Schuchert, MD, Brian L

Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy

(A) Lymph node priming phase: recognition of major histocompatibility complex (MHC) by T-cell receptor (TCR), coactivating CD 28/B7 pathway activation.

Cytokine Gene Therapy for Malignant Pleural Mesothelioma

Esophagectomy for T1 Esophageal Cancer: Outcomes in 100 Patients and Implications for Endoscopic Therapy Arjun Pennathur, MD, Andrew Farkas, BA, Alyssa.

Something in the Air: Hyperoxic Conditioning of the Tumor Microenvironment for Enhanced Immunotherapy Robert D. Leone, Maureen R. Horton, Jonathan D.

Differential pathway regulation in advanced idiopathic pulmonary fibrosis (IPF) lung. a) Metacore analyses of pathway enrichment in IPF versus control.

Presentation transcript:

Targeting Immune Checkpoints in Esophageal Cancer: A High Mutational Load Tumor Rajeev Dhupar, MD, Lauren Van Der Kraak, PhD, Arjun Pennathur, MD, Matthew J. Schuchert, MD, Katie S. Nason, MD, James D. Luketich, MD, Michael T. Lotze, MD The Annals of Thoracic Surgery Volume 103, Issue 4, Pages 1340-1349 (April 2017) DOI: 10.1016/j.athoracsur.2016.12.011 Copyright © 2017 The Society of Thoracic Surgeons Terms and Conditions

Fig 1 Normal activation and inactivation of immune cells. (Upper panel) A CD8+ T-cell can be activated after interaction with an antigen-presenting cell, after which the T-cell can kill cancer cells. (Lower panel) However, a natural “braking” system (ie, negative feedback) to prevent an overwhelming immune response occurs when checkpoint proteins inactivate these T-cells. (CD8+ = cluster of differentiation 8; MHC = major histocompatibility complex; TCR = T-cell receptor.) The Annals of Thoracic Surgery 2017 103, 1340-1349DOI: (10.1016/j.athoracsur.2016.12.011) Copyright © 2017 The Society of Thoracic Surgeons Terms and Conditions

Fig 2 Cancer cells “hijacking” checkpoint proteins to evade the immune system. (Upper panel) Some cancer cells express checkpoint proteins, which inactivate T-cells and allow the cancer cells to evade the immune system and escape death. (Lower panel) However, checkpoint inhibitor proteins can block this method of evasion by the cancer cells, thereby allowing the immune system to kill cancer cells. (CD8+ = cluster of differentiation 8.) The Annals of Thoracic Surgery 2017 103, 1340-1349DOI: (10.1016/j.athoracsur.2016.12.011) Copyright © 2017 The Society of Thoracic Surgeons Terms and Conditions

Fig 3 Literature search performed. Papers examined were restricted to those in English and those with either adenocarcinoma or squamous carcinoma of the esophagus. (B7-DC = B7-dendritic cell; B7-H1 = B7-homolog 1; CTLA-4 = cytotoxic T-lymphocyte associated protein 4; DC = dendritic cell; IL-2 = interleukin-2; LAG3 = lymphocyte activation gene 3; PD-L1 = programmed cell death ligand 1; PD-1 = programmed cell death protein 1; TIGIT = T-cell immunoglobulin and ITIM domain; TIM3 = T-cell immunoglobulin mucin 3.) The Annals of Thoracic Surgery 2017 103, 1340-1349DOI: (10.1016/j.athoracsur.2016.12.011) Copyright © 2017 The Society of Thoracic Surgeons Terms and Conditions

Fig 4 Proposed key pathways that effect PD-L1/2 expression in esophageal adenocarcinoma. In esophageal cancer, expression of PD-L1 and PD-L2 is likely modulated by numerous environmental factors (chemotherapy, radiation, or other inflammatory states) that are currently not well defined. Stress-responsive receptors and transcription factors (such as interferon regulatory factors/toll-like receptors) and adaption mechanisms (such as autophagy) contribute to tumor survival by enhancing surface expression of checkpoint inhibitors. Understanding these interactions will be critical to determine how to improve treatments that allow unleashing of the immune system to overcome tumor defense mechanisms such as PD-L1/2 expression, expression of immunosuppressive cytokines, and protective autophagy. (CD4+ = cluster of differentiation 4; CD8+ = cluster of differentiation 8; CD 80 = cluster of differentiation 80; CTLA-4 = cytotoxic T-lymphocyte associated protein 4; DC = dendritic cell; HMGB1 = high mobility group box 1; IFN = interferon; IL = interleukin; IRF = interferon regulatory factor; PD-L1 = programmed cell death ligand 1; PD-L2 = programmed cell death ligand 2; PD-1 = programmed cell death protein 1; RAGE = receptor for advanced glycation end products; TGF = transforming growth factor; TLR4 = toll-like receptor 4; Treg = regulatory T-cell.) The Annals of Thoracic Surgery 2017 103, 1340-1349DOI: (10.1016/j.athoracsur.2016.12.011) Copyright © 2017 The Society of Thoracic Surgeons Terms and Conditions