Immunotherapy of Cancer

 
 
Academic Press
  • 1. Auflage
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  • erschienen am 29. Juli 2015
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  • 392 Seiten
 
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978-0-12-802554-3 (ISBN)
 

Immunotherapy of Cancer provides information on cancer research related to inflammation and immunity, containing outstanding reviews by experts in the field. It is suitable for researchers and students who have an interest in cancer immunobiology.


  • Provides information on cancer research, including outstanding and original reviews
  • Covers the current progress and emerging concepts in cancer inflammation, immunology, and immunotherapy
  • Suitable for researchers and students studying, and interested in, the field of immunotherapy for cancer
  • Ideal for those studying cancer inflammation, tumor immunology, cancer immunotherapy, dendritic cell, antigen presentation, immune checkpoint, myeloid-derived suppressor cells, macrophages, and tumor environments
0065-230X
  • Englisch
  • San Diego
  • |
  • USA
Elsevier Science
  • 10,69 MB
978-0-12-802554-3 (9780128025543)
0128025549 (0128025549)
weitere Ausgaben werden ermittelt
  • Front Cover
  • Immunotherapy of Cancer
  • Copyright
  • Contents
  • Contributors
  • Preface
  • Chapter One: The New Era of Cancer Immunotherapy: Manipulating T-Cell Activity to Overcome Malignancy
  • 1. Introduction
  • 2. Modulation of T-Cell Activity with mAbs
  • 2.1. CTLA-4
  • 2.2. PD-1/PD-L1
  • 2.3. LAG-3
  • 2.4. TIM-3
  • 2.5. TIGIT
  • 2.6. BTLA
  • 2.7. 4-1BB
  • 2.8. GITR
  • 2.9. CD40
  • 2.10. OX40
  • 3. Adoptive T-Cell Transfer
  • 3.1. TIL Therapy
  • 3.2. Transgenic TCRs
  • 3.3. CAR Therapy
  • 4. Small Molecules for Immune Modulation
  • 4.1. Indoleamine 2,3-Dioxygenase
  • 4.2. PI3 Kinase
  • 4.3. Mammalian Target of Rapamycin
  • 4.4. BRAF
  • 5. Other Approaches
  • 5.1. Radiotherapy and Immunomodulatory Effects of Radiation on Tumors
  • 5.2. Combination of Radiation Therapy with Immunotherapy
  • 5.3. Oncolytic Viruses
  • 6. Conclusion
  • Acknowledgments
  • References
  • Chapter Two: Immune Targeting of Tumor Epithelial-Mesenchymal Transition via Brachyury-Based Vaccines
  • 1. Introduction
  • 2. Tumor EMT
  • 2.1. EMT and Tumor Invasiveness
  • 2.2. EMT and Tumor Stemness
  • 2.3. EMT and Tumor Resistance
  • 3. Targeting of EMT
  • 3.1. EMT Transcription Factors
  • 3.2. Advantage of an Immune Approach Against EMT
  • 3.3. Immunotherapeutic Approaches Against Cancer
  • 3.3.1. Cancer Vaccines
  • 3.3.2. Immune Checkpoint Inhibition
  • 3.4. The Choice of Tumor Antigen
  • 3.5. Brachyury as a Tumor Antigen
  • 3.6. Therapeutic Vaccines Against Brachyury
  • 3.6.1. Yeast-Based Brachyury Vaccine
  • 3.6.2. Poxvirus-Based Brachyury Vaccine
  • 4. Overcoming Potential Tumor Immune Resistance
  • 5. Concluding Remarks
  • Acknowledgments
  • References
  • Chapter Three: Myeloid-Derived Suppressor Cells: Critical Cells Driving Immune Suppression in the Tumor Microenvironment
  • 1. Myeloid-Derived Suppressor Cell History
  • 1.1. Mouse MDSCs
  • 1.2. Human MDSCs
  • 2. MDSC Development and Suppressive Functions Are Induced by Inflammation
  • 2.1. Vascular Endothelial Growth Factor
  • 2.2. Granulocyte-Macrophage Colony-Stimulating Factor and Granulocyte Colony-Stimulating Factor
  • 2.3. Prostaglandin E2 and Cyclooxygenase 2
  • 2.4. CCAAT/Enhancer Binding Protein ß and C/EBP Homologous Protein
  • 2.5. Complement Component C5a
  • 2.6. S100A8/A9
  • 2.7. High-Mobility Group Box 1
  • 2.8. IL-1ß, IL-6, and Indoleamine 2,3-Dioxygenase
  • 2.9. IL-17
  • 3. MDSC Are Regulated by Multiple Molecular Mechanisms
  • 3.1. Signal Transducer and Activator of Transcription 1
  • 3.2. Signal Transducer and Activator of Transcription 3 and 6
  • 3.3. Nuclear Factor Kappa-Light-Chain-Enhancer
  • 3.4. Interferon Regulatory Factor-8
  • 3.5. Notch
  • 3.6. Hypoxia-Inducible Factor-1 Alpha
  • 3.7. MicroRNAs
  • 3.8. MDSC Turnover
  • 4. MDSCs Utilize a Network of Effector and Signaling Molecules to Modulate the Inflammatory Milieu and Decrease Immune Su ...
  • 4.1. MDSC Depletion of Amino Acids
  • 4.2. MDSC Production of NO
  • 4.3. MDSC Production of ROS
  • 4.4. MDSCs Inhibit T Cell Migration by Downregulating L- and E-Selectins
  • 4.5. MDSCs Express Programmed Death-Ligand 1
  • 4.6. MDSCs Induce Tregs and Th17 Cells
  • 4.7. MDSCs Impair NK Cell-Mediated Cytotoxicity
  • 4.8. Cross Talk Between MDSCs, Macrophages, Tumor Cells, and MCs Enhances Inflammation and Promotes MDSC Suppressive Activity
  • 5. MDSCs in Noncancer Settings
  • 6. Therapeutic Targeting of MDSCs
  • 7. Conclusions
  • References
  • Chapter Four: Phagocytes as Corrupted Policemen in Cancer-Related Inflammation
  • 1. Introduction
  • 2. Origin and Functions of TAMs
  • 3. Macrophages in Complement-Mediated, PTX3-Regulated Tumor Promotion
  • 4. The Yin Yang of TAMs in Anticancer Therapy
  • 5. Neutrophils and Cancer
  • 5.1. Neutrophil Recruitment and Their Prognostic Significance in Tumors
  • 5.2. Neutrophils in Tumor Initiation and Progression
  • 5.3. Neutrophils in Tumor Progression: Angiogenesis and Metastatic Behavior Modulation
  • 5.4. Neutrophil Plasticity and Heterogeneity in Cancer
  • 5.5. Neutrophils, TANs, and MDSCs
  • 6. Concluding Remarks
  • Acknowledgment
  • References
  • Chapter Five: Tumor-Elicited Inflammation and Colorectal Cancer
  • 1. Introduction
  • 2. Cytokines in CRC Development
  • 2.1. Tumor-Necrosis Factor
  • 2.2. Interleukin-10
  • 2.3. Transforming Growth Factor-ß
  • 2.4. IL-6 and IL-11
  • 2.5. IL-21
  • 2.6. IL-22
  • 2.7. IL-23 and IL-17 Axis of Inflammation
  • 3. Commensal Flora, Barrier Defect, and Tumor-Elicited Inflammation
  • 4. Concluding Remarks and Therapeutic Outlook
  • References
  • Chapter Six: Therapeutic Lymphoid Organogenesis in the Tumor Microenvironment
  • 1. Introduction
  • 2. Development of TLSs in Chronically Diseased Tissues
  • 2.1. TLSs: Organizational Structure
  • 3. TLSs in Cancer: Clinical Correlates of Disease Progression and Response to Treatment
  • 4. Cues for TLS Development
  • 4.1. The Requirement for Lymphotoxin Signaling in the Evolution of TLSs in the TME
  • 4.2. EnLIGHTening Protective Immunity in TLSs
  • 4.3. The Importance of CCR7 Agonists for TLS Evolution in the TME
  • 4.4. The Importance of CXCR5 Agonists in TLS Evolution
  • 5. Therapeutic Manipulation of TLSs in Cancer Patients: Establishing a Paradigm for Antitumor Efficacy
  • 6. Importance of IL-1 Family Member Cytokines in Establishing Therapeutic TLSs
  • 6.1. IL-36 as an Early Inflammatory Mediator of Lymphoid Organogenesis in Tissues, Including Cancer
  • 7. Conclusions and Future Directions for Clinical Translation
  • Acknowledgment
  • References
  • Chapter Seven: The Tumor Macroenvironment: Cancer-Promoting Networks Beyond Tumor Beds
  • 1. Introduction
  • 2. Interactions Between the TME and the Bone Marrow
  • 2.1. Pathological Myelopoiesis Promotes Malignant Progression
  • 2.2. Tumor-Derived Secreted Factors Promote the Expansion of Immunosuppressive MDSCs
  • 3. Subsets of Myeloid Precursors Pathologically Mobilized in Tumor-Bearing Hosts
  • 4. Lineage-Committed Myeloid Populations in the TME
  • 5. Metastatic Spreading and the Metastatic Niche
  • 5.1. Tumor-Mediated Influence on the Premetastatic Niche: Preparation for Tumor Seeding at Distal Sites
  • 5.2. Tissue-Specific Properties in the Formation of Metastatic Niches
  • 6. Role of the Microbiota in Tumor Progression
  • 6.1. Commensal Microbiota Are Required for Effective Antitumor Immune Responses for Extraintestinal Tumors
  • 6.2. The Role of Microbe-Induced Inflammation During Malignant Progression
  • 7. Distally Produced Hormones Influence Tumor Progression
  • 7.1. Estrogens and the Tumor Macroenvironment (Estrone, Estradiol, and Estriol)
  • 7.2. Androgens in the Tumor Macroenvironment (Testosterone and Dihydrotestosterone)
  • 7.3. Insulin and Insulin-Like Growth Factor-I in the Tumor Macroenvironment
  • 8. Conclusions
  • Acknowledgments
  • References
  • Chapter Eight: Control of CD8 T-Cell Infiltration into Tumors by Vasculature and Microenvironment
  • 1. Prognostic Significance of Immune Cell Representation in Tumors
  • 2. CD8 T-Cell Representation in Tumors as a Predictive Marker of Responsiveness to Therapy
  • 3. Determinants of CD8 T-Cell Representation in Tumors and Other Tissues
  • 3.1. Trafficking of Effector T-Cells into Tissues
  • 3.2. Trafficking of Effector T-Cells into Tumors
  • 3.3. Positive Feedback Loops in Vascular Ligand Expression
  • 3.4. Mechanical Properties of Vasculature
  • 4. Tumors Develop HEV-Like Vasculature
  • 4.1. Control of HEV in Lymph Nodes and Tertiary Lymphoid Structures
  • 4.2. Control of the Development of HEV-Like Vessels in Tumors
  • 4.3. Association of Tumor HEV with TLS
  • 4.4. Tumor-Associated HEV-Like Vessels Support Enhanced Antitumor Immunity
  • 5. Altering the Tumor Vasculature to Support Enhanced Entry of Naïve and Effector T-Cells
  • 5.1. Rationale for Modifying Tumor-Associated Vasculature
  • 5.2. Strategies for Modifying Tumor-Associated Vasculature
  • References
  • Chapter Nine: Scavenger Receptors: Emerging Roles in Cancer Biology and Immunology
  • 1. Introduction
  • 2. Scavenger Receptors in Cancer Immunobiology
  • 2.1. Class A Scavenger Receptor
  • 2.1.1. Scavenger Receptor Class A
  • 2.1.2. Macrophage Receptor with Collagenous Structure
  • 2.1.3. Scavenger Receptor Class A, Member 3 and Member 5 (SCARA3 and SCARA5)
  • 2.2. Class B Scavenger Receptor
  • 2.2.1. Thrombospondin Receptor CD36
  • 2.2.2. Scavenger Receptor Class B, Member 1 (SR-BI)
  • 2.3. Class D Scavenger Receptor
  • 2.4. Class E Scavenger Receptor
  • 2.4.1. Lectin-Like Oxidized LDL Receptor 1
  • 2.4.2. ß-Glucan Receptor Dectin-1
  • 2.5. Class F Scavenger Receptor
  • 2.6. Class G Scavenger Receptor
  • 2.7. Class H Scavenger Receptor
  • 2.8. Class I Scavenger Receptor
  • 2.9. Class J Scavenger Receptor
  • 3. Scavenger Receptors in Cancer Therapy
  • 3.1. Scavenger Receptor-Based Delivery of Antineoplastic Drugs
  • 3.2. Scavenger Receptors and Immune Modulation Therapy
  • 4. Concluding Remarks
  • Acknowledgments
  • References
  • Index
  • Color Plate
Chapter One

The New Era of Cancer Immunotherapy


Manipulating T-Cell Activity to Overcome Malignancy


Danny N. Khalil*,; Sadna Budhu*; Billel Gasmi*; Roberta Zappasodi*; Daniel Hirschhorn-Cymerman*; Tamar Plitt*; Olivier De Henau*,; Dmitriy Zamarin*,,§; Rikke B. Holmgaard*; Judith T. Murphy*; Jedd D. Wolchok*,,§; Taha Merghoub*,,1    * Ludwig Collaborative and Swim Across America Laboratory, Memorial Sloan Kettering Cancer Center, New York, USA
┼ Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA
╬ Department of Medical Oncology, Jules Bordet Institute, Universite Libre De Bruxelles, Brussels, Belgium
§ Weill Cornell Medical College, New York, USA
1 Corresponding author: email address: Merghout@mskcc.org

Abstract


Using the immune system to control cancer has been investigated for over a century. Yet it is only over the last several years that therapeutic agents acting directly on the immune system have demonstrated improved overall survival for cancer patients in phase III clinical trials. Furthermore, it appears that some patients treated with such agents have been cured of metastatic cancer. This has led to increased interest and acceleration in the rate of progress in cancer immunotherapy. Most of the current immunotherapeutic success in cancer treatment is based on the use of immune-modulating antibodies targeting critical checkpoints (CTLA-4 and PD-1/PD-L1). Several other immune-modulating molecules targeting inhibitory or stimulatory pathways are being developed. The combined use of these medicines is the subject of intense investigation and holds important promise. Combination regimens include those that incorporate targeted therapies that act on growth signaling pathways, as well as standard chemotherapy and radiation therapy. In fact, these standard therapies have intrinsic immune-modulating properties that can support antitumor immunity. In the years ahead, adoptive T-cell therapy will also be an important part of treatment for some cancer patients. Other areas which are regaining interest are the use of oncolytic viruses that immunize patients against their own tumors and the use of vaccines against tumor antigens. Immunotherapy has demonstrated unprecedented durability in controlling multiple types of cancer and we expect its use to continue expanding rapidly.

Keywords

Immunotherapy

Checkpoint blockade

Costimulation

Adoptive cell therapy

CAR T cells

1 Introduction


Despite much recent attention to the field of cancer immunotherapy (Couzin-Frankel, 2013), the idea of recruiting the immune system against cancer predates our knowledge of the genetic basis of cancer and even modern genetics. The reason for the relative lack of attention to the field is debatable, but likely is in part due to important developments in other modes of cancer therapy such as surgery, radiation, cytotoxic chemotherapy, and most recently targeted therapy. While there are indications that ancient civilizations intentionally transferred microbes into tumors to control their growth, thereby unknowingly harnessing the immune system, modern cancer immunotherapy can be traced back to Dr. William Coley, a surgeon working in New York City who began treating cancer patients by injecting live Streptococcus pyogenes intratumorally after learning of a patient with prolonged remission of recurrent sarcoma after severe erysipelas (Coley, 1991).

In the century since the work of Coley, research in the field of cancer immunotherapy has continued mostly outside the spotlight of mainstream cancer research. While the first data from a phase III clinical trial demonstrating improved overall survival among patients with advanced cancer attributable to immunotherapy would not come until 2010 (Hodi et al., 2010), there were several instructive successes in the interim that have impacted standard of care. Cytokine therapy has been the most important such therapy for systemic disease. Interleukin-2 treatment has resulted in durable responses for patients with metastatic renal cell carcinoma and melanoma (Rosenberg, 2014; Rosenberg et al., 1994). Interferon-a has been developed for the treatment of melanoma, renal cell carcinoma, AIDS-related Kaposi sarcoma, follicular lymphoma, and hairy cell leukemia (Gajewski & Corrales, 2015; Jonasch & Haluska, 2001). The knowledge gained from the experience with these agents has been invaluable, and their role in controlling cancer remains an area of active research. They have demonstrated the extreme manifestations of attempting to engage the immune system in treating cancer, as patients have developed both severe toxicity as well as deep, durable disease control. In many ways, it was these results that motivated the strong interest in engaging the immune system with greater specificity. This resulted in a concerted effort to develop therapeutic cancer vaccines that dominated the field for more than a decade. The fact that this has yet to result in the approval of vaccination for the treatment of human cancer is instructive in itself, and while this remains an exciting field of translational cancer research, it suggests that educating the immune system to recognize disease-specific antigens, a highly effective method in preventing infectious disease, may not address the crucial barriers preventing a healthy immune system from eradicating tumors.

Although cancer immunotherapy has largely focused on the systemic control of cancer, it is important to recognize its historic contribution in the treatment of localized disease. Topical imiquimod, a TLR7 agonist, is indicated for the treatment of superficial basal cell carcinoma (Beutner et al., 1999); and the tuberculosis vaccine Bacillus Calmette-Guérin is used intravesically in the treatment of nonmuscle-invasive bladder cancer (Brandau & Suttmann, 2007).

Other standard treatments for cancer that are not always categorized as "immunotherapy" also rely, to a greater or lesser extent, on the immune system. The graft-versus-leukemia effect of allogeneic bone-marrow transplant is well known (Horowitz et al., 1990). Antigen presentation by dendritic cells (DCs) seems to be necessary for the potentially curative effect of extracorporeal photopheresis in cutaneous T-cell lymphoma (Edelson, 1999). The efficacy of antitumor monoclonal antibodies (mAbs) such as rituximab, trastuzumab) partially depends on immune-mediated destruction of targeted malignant cells even when the target is a growth factor receptor (Horlock et al., 2009; Tokuyama et al., 2008). Similarly, small molecules, including those developed to block cancer-cell signaling pathways (e.g., vemurafenib), also have profound effects on the antitumor immune response (Su et al., 2012). Along these lines, it is important to recognize that the immunologic impact of surgery, radiation therapy, and cytotoxic chemotherapy is also significant in some cases (Apetoh et al., 2007; Vittimberga, Foley, Meyers, & Callery, 1998).

The clinical success of immune checkpoint blockade and genetically engineered T cells has drawn tremendous interest. This has served not only to accelerate studies of how these tools can be implemented and improved, but it has also opened the door to investigation of new classes of immunotherapies, many of which are already in active clinical development. In this piece we provide an overview of the current state of therapeutic immune modulation in cancer, highlighting areas that we feel hold particular promise. We lay out the role of mAbs in blocking immune checkpoints and activating costimulatory molecules. This is followed by a description of adoptive T-cell therapy. We then describe a set of small-molecule inhibitors that are potentially potent immunomodulators. Finally, we review the place of radiotherapy and oncolytic virus therapy in mediating anticancer immune activity.

2 Modulation of T-Cell Activity with mAbs


After decades of research on educating the immune system to recognize specific antigens associated with cancers, primarily in the form of therapeutic anticancer vaccines, a very different approach in which inhibitory or activating immune cell receptors are targeted has recently gained interest (Fig. 1). This method uses mAbs to block inhibitory receptors or to activate stimulatory receptors on T cells and other immune cells (Table 1). This approach has proved sufficient to mediate robust antitumor activity in the absence of an agent to direct the immune response to specific antigens.

Figure 1 Overview of immunomodulatory cell-surface molecules on tumor cells, conventional T cells, regulatory T cells, and antigen-presenting cells: T-cell receptors to the left of the dashed line are inhibitory and those to the right are stimulatory. Agonist mAbs against stimulatory receptors and blocking mAbs against inhibitory receptors have demonstrated robust antitumor activity in clinical and preclinical studies. From PMID: 20307208, 22961161, 22261959, 25743219, 23334208,...

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