Immune Therapy for Pancreatic and Colon Cancers

1st Edition - November 26, 2024
Imprint: Academic Press
Editors: Ganji Purnachandra Nagaraju, Soumya Dakshinamurthy, Sarfraz Ahmad
Language: English
Paperback ISBN:
9 7 8 - 0 - 4 4 3 - 2 4 7 4 2 - 2
eBook ISBN:
9 7 8 - 0 - 4 4 3 - 2 4 7 4 3 - 9

Immune Therapy for Pancreatic and Colon Cancer expands the knowledge on pathways, immune modulators, immune check points, and monoclonal antibodies that can lead to approp… Read more

Immune Therapy for Pancreatic and Colon Cancers

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Immune Therapy for Pancreatic and Colon Cancer expands the knowledge on pathways, immune modulators, immune check points, and monoclonal antibodies that can lead to appropriate cancer treatment. With a strong focus on the development of immune therapies to improve the survival rates of pancreatic and colon cancer, this book also shows the latest trends in immune targeted approaches for cancer treatment. Sections describe the role of and the immune response to pancreatic and colon cancer, gives insights to past and current immunotherapies, including metabolic reprogramming, immune blockade therapy and immune modulation.

This book is a valuable resource for health professionals, scientists and researchers, students, and all those who wish to broaden their knowledge of the advances in immunotherapy in pancreatic and colon cancer, inspire them and guide their design of novel experimental projects and translational studies.

Immune Therapy for Pancreatic and Colon Cancers
Cover image
Title page
Table of Contents
Copyright
Contributors
About the Editors
Preface
Acknowledgment
Chapter 1 Introduction to colon and pancreatic cancers
Abstract
Keywords:
Declarations
Colorectal cancer
Introduction
Epidemiology of colorectal cancer
Risk factors and pathogenesis of colorectal cancer
Diagnosis of colorectal cancer
Pancreatic cancer
Introduction
Epidemiology of pancreatic Cancer
Diagnosis of pancreatic cancer
References
Chapter 2 An overview of imaging in pancreatic cancer
Abstract
Keywords:
Conflict of interest
Introduction
Epidemiology, risk factors, and prognosis
Challenges in early diagnosis and the importance of imaging
Overview of the imaging modalities
Imaging Modalities
CT scan
MRI/MRCP
Endoscopic ultrasound
PET scan
Imaging for diagnosis and staging
Determining resectability
Quantitative imaging biomarkers
Imaging surveillance posttreatment
Surveillance guidelines
Screening high-risk groups
Emerging imaging techniques
Summary and conclusions
References
Chapter 3 Colorectal cancer: Understanding the pathophysiology, screening options and treatment approaches
Abstract
Keywords:
Conflict of interest
Introduction
Etiology and pathophysiology
Screening
Colonoscopy: The benchmark screening test
Treatment
Surgical management of CRC
Surgical goals and techniques
Systemic therapy for CRC
Emerging treatment strategies
Conclusion
References
Chapter 4 Tumor microenvironment of colorectal cancer
Abstract
Keywords:
Conflict of interest
Introduction
Components of tumor microenvironment
Cellular components in the TME
Noncellular components in the TME
Conclusion
References
Chapter 5 Role of PD-1 as an immunotherapeutic target in GI cancers
Abstract
Keywords:
Introduction
Immunotherapy
Types of immunotherapies
PD-1
PD-based therapy for pancreatic cancer
PD-based therapy for colon cancer
Clinical trials
Limitations
Conclusion
References
Chapter 6 Immunotherapy in colorectal cancer: Understanding the PD-1 and CTLA-4 targeted therapies for MSI-H/dMMR tumors
Abstract
Keywords:
Conflict of interest
Introduction
CRC and immune evasion
Checkpoint proteins and inhibitors in CRC
PD-1 and its inhibitors
CTLA-4 and its inhibitor
Toxicity of immunotherapy
Conclusion
References
Chapter 7 Single-cell analysis of colon cancer: Novel insight into drug resistance and immunotherapy
Abstract
Keywords:
Acknowledgment
Introduction
scRNA-seq analyses of immune cells in CC
scRNA-seq analyses of tumor-associated fibroblasts in CC
scRNA-seq analyses of tumor cells in CC
Conclusion
References
Chapter 8 Delivery strategies of immunotherapies in the treatment of colorectal cancer
Abstract
Keywords:
Conflict of interest
Introduction
Cancer immunotherapy
Delivery strategies for immunotherapy
Nanoparticles
Extracellular vesicles
Implantable and injectable scaffolds
Cell-based delivery systems
Conclusion
References
Chapter 9 Therapeutic role of immune cells against colon cancer
Abstract
Keywords
Acknowledgments
Conflict of interest
Introduction
Immune cells involved in colon cancer therapy
Tumor-infiltrating lymphocytes
Natural killer cells
Dendritic cells
Therapeutic strategies utilizing immune cells
Adoptive cell therapy
Immune checkpoint inhibitors
Vaccination strategies
Future perspectives
Conclusion
References
Chapter 10 The potential of biosimilars in the treatment of colorectal cancer: Focus on bevacizumab
Abstract
Keywords:
Authors contributions
Introduction
Targeted therapies: The VEGF pathway
Molecular mechanism of VEGF/VEGFR signaling pathway
Bevacizumab (Avastin®)
The role of bevacizumab in the treatment of mCRC
Limits to bevacizumab use
Cost-effectiveness of biosimilars
The concept of biosimilars
Definition and general considerations
Demonstrating biosimilarity
Extrapolation
FDA-approved bevacizumab biosimilars for the treatment of metastatic colorectal cancer
ABP215 (bevacizumab-awwb)
PF-06439535 (Bevacizumab-bvzr)
CT-P16 (Bevacizumab-adcd)
Conclusion and further perspectives
References
Chapter 11 Understanding colorectal cancer, screening, and treatment
Abstract
Keywords:
Conflicts of interest
Introduction
Hereditary colorectal cancer syndromes
Screening
Clinical presentation
Treatment of colorectal cancers
Metastatic colorectal cancer
KRAS-targeted therapy in colorectal cancers
Human epidermal growth factor receptor 2
Immunotherapies in colorectal cancers
Monoclonal antibodies
Effectiveness of immune checkpoint inhibitor therapies in colorectal cancers
Anticancer vaccines for CRC
Cost-effectiveness of treatments in colorectal cancers
Summary
References
Chapter 12 Challenges in immunotherapy for PDAC: Overcoming immune resistance and enhancing treatment strategies
Abstract
Keywords:
Conflict of interest
Introduction
Strategies in PDAC
Immunotherapy approaches
Immune checkpoint inhibitors
PD-1/PD-L in PDAC
Adoptive cell therapy
Cancer vaccines
Conclusion
References
Chapter 13 Unveiling the orchestration of T-cell dynamics: A comprehensive examination of their crucial role in revolutionizing immunotherapy for pancreatic and colon cancers
Abstract
Keywords:
Introduction
Sentinel guardians of immunity
Effector functions in tumor eradication
Memory T-cells: Sustaining immunological vigilance
Regulatory T-cells (Tregs): Balancing immune responses
Overcoming T-cell exhaustion
Immunomodulatory cytokines and chemokines
Interrogating T-cell responses in tumor microenvironments
Deciphering T-cell subtypes and their roles
Investigating T-cell exhaustion and strategies for reinvigoration
Unveiling interactions with other immune components [29]
Implications for tailored immunotherapies
Methodology
Patient selection criteria and demographics
Techniques employed for T-cell profiling and characterization
Analysis of tumor microenvironment factors influencing T-cell functionality
Extracellular matrix remodeling [47]
Immune checkpoint expression profiling [47]
Metabolic landscape mapping [48]
Inflammatory cytokine profiling [49]
Immunosuppressive cell infiltration analysis [50]
Gut microbiome influence investigation [51]
Three-dimensional (3D) organoid models [52]
T-cell subtypes and their significance
Regulatory T-cells (Tregs) and their impact on immunotherapy
Tregs as orchestrators of immune tolerance [64]
Spatial distribution and infiltration patterns
Tregs and immunosuppressive signaling pathways
Treg plasticity and adaptation [67]
Impact of Tregs on cytotoxic T-cell functionality
Tregs in the context of checkpoint inhibitors
Targeting Tregs for enhanced immunotherapy
Memory T-cells: Unveiling the long-term immunological memory
T-cell exhaustion and overcoming immune suppression
Identification of exhausted T-cell markers
Strategies to reinvigorate exhausted T-cells for improved antitumor response
Interplay of T-cells with other immune components
Investigating interactions with dendritic cells, macrophages, and NK cells
Cytokine networks influencing T-cell behavior within tumor microenvironments
Impact of the gut microbiome on T-cell functionality
Case studies
Case study: Immunotherapy-resistant pancreatic cancer reversed by T-cell reinvigoration
Case study: Gut microbiome modulation enhances immunotherapy efficacy in colon cancer
Case study: Targeted cytokine therapy reverses T-cell dysfunction in pancreatic cancer
Future perspectives
Personalized T-cell therapies
Integration of artificial intelligence (AI)
Microbiome-based precision medicine
Ethical considerations
Informed consent and genomic data
Equity in access to innovative therapies
Transparency in clinical trials
Conclusion
References
Chapter 14 Role of T-cells in immunotherapy of pancreatic and colon cancers
Abstract
Keywords:
Introduction
Cancer immunotherapy
CAR-T cell-based immunotherapy
CAR-T cells-pancreatic cancer
CAR-T cells-colon cancer
T-cell cancer therapy applications
Clinical trials
Limitations
Conclusion
References
Chapter 15 Role of platelets in immunomodulation in pancreatic and colorectal cancers
Abstract
Keywords:
Conflict of interest
Introduction
Notable common hallmarks of colorectal and pancreatic cancers with likely cancer-promoting roles for platelets
How cancer cells affect platelets
Tumor cells can activate platelets
Tumor cells increase platelet production
Tumor cells alter platelet RNA and protein profiles
How platelets support tumor growth and invasion
The immunomodulatory effects of platelets on the primary tumor microenvironment
The impact of platelets on tumor cell epithelial-mesenchymal transition
The impact of platelets on tumor angiogenesis
The immunoprotective effects of platelets on tumor cells in circulation
The effect of platelets in the recruitment of prometastatic leukocytes
Potential for antiplatelet agents as a therapeutic strategy in combination with immunotherapy in colorectal and pancreatic cancers
Concluding remarks and future perspectives
References
Chapter 16 The role of circulating tumor cells in the immunotherapy of pancreatic and colon cancers
Abstract
Keywords:
Introduction
Definition of CTCs
Process of CTC detection and isolation
Characterization techniques of CTCs
Importance of CTCs in pancreatic and CCs
Role of CTCs in pancreatic and CCs
Clinical implications and treatment strategies
Role of CTCs in guiding immunotherapy approaches for pancreatic and CCs (Table 6)
Role of CTCs in immunotherapy resistance
Tumor microenvironment and T-cell trapping
Potential of natural killer (NK) cells in immunotherapy
CTCs as a tool for patient stratification
CTCs and patient stratification in pancreatic cancer
CTCs and patient stratification in CRC
Assessing immune cell infiltration within CTCs
Immune cell infiltration as an indicator of the immune microenvironment
Immune cell infiltration and tumor aggression
Immune cell infiltration and prognosis
Immune cell infiltration and response to immunotherapy
Identifying tumor antigen expression on CTCs
Monitoring CTC changes during immunotherapy
Immunotherapeutic strategies targeting CTCs (Table 9)
Targeting CSF1R signaling to reprogram macrophage responses
Targeting the CCL2/CCR2 axis and inflammatory monocytes
Targeting VISTA expressed on CD68+ macrophages
Antibody-based targeting of CTC antigens
Nectin-4 as a potential target in pancreatic and CC
Adoptive cell therapies using CTC-derived immune cells (Table 10)
ACTs using CTC-derived immune cells in pancreatic cancer
ACTs using CTC-derived immune cells in CC
Activating immune responses against CTCs using immunomodulatory agents
Immunotherapy converts nonimmunogenic pancreatic tumors into immunogenic foci of immune regulation
Electrochemotherapy with bleomycin induces hallmarks of immunogenic cell death in murine CC cells
Immunomodulatory and antitumor effects of type I interferons (IFNs) and their application in cancer therapy
Role of immune cells in pancreatic cancer from bench to clinical application
Challenges and future perspectives
Technical limitations in CTC detection and isolation
Heterogeneity of CTC populations
Heterogeneity of cancer-associated fibroblasts (CAFs) in PDAC
Heterogeneity of CTCs in PDAC
Heterogeneity of CTCs in colon tumors
Harnessing CTCs for personalized immunotherapy
Immunogenic tumor antigens in successful immunotherapy
Emerging opportunities and challenges in cancer immunotherapy
Immunogenic cell death for cancer immunotherapy
Enhanced detection of neoantigen-reactive T cells
Neoantigen identification strategies for personalized immunotherapy
mRNA therapeutics in cancer immunotherapy
Precision medicine for urothelial bladder cancer
Recapitulation of the importance of CTCs in immunotherapy for pancreatic and CCs
Mismatch repair deficiency (MMR) as a biomarker
Metabolic syndrome and cancer risk
Pioglitazone use and cancer risk
Tumor mutation load (TML) and immunotherapy response
CD47 blockade and tumor cell phagocytosis
Adiposity and cancer risk
CTCs as prognostic factors
Combination therapy with PD-L1 and TGF-β blockade
Survivin-2B80-88 vaccination protocol
Intraperitoneal catumaxomab for peritoneal carcinomatosis
Conclusion
References
Chapter 17 Vaccine-based immunotherapy for pancreatic and colon cancers
Abstract
Keywords:
Introduction
Immunotherapy
Vaccine based immunotherapy
Applications of vaccine-based immunotherapy in cancer
FDA approved cancer vaccines
Vaccine based therapy for pancreatic cancer
Types of vaccine-based therapy for pancreatic cancer
Tumor-associated antigens and tumor specific vaccine therapy
Dendritic cell vaccines
Peptide-based vaccines and adjuvants
mRNA vaccine
Vaccine-based therapy for colon cancer
Tumor-associated antigens and tumor specific vaccine therapy
Dendritic cell vaccines
Peptide-based vaccines and adjuvants
Viral vector vaccines
Conclusion
References
Chapter 18 Overcoming immunotherapeutic drug resistance in pancreatic and colon cancers
Abstract
Keywords:
Introduction
Immunotherapeutic drug resistance in pancreatic and colon cancers
Mechanisms of immunotherapy resistance
Specific immunotherapy resistance in pancreatic cancer
Specific immunotherapy resistance in colon cancer
Overcoming immunotherapy resistance
Combination therapies in pancreatic cancer
Combination therapies in colon cancer
Personalized medicine
Cancer vaccines
Clinical trials to overcome resistance
Examples of monotherapy
Immune checkpoint inhibitors
PD-1 inhibitors
CTLA-4
PD-L1
Novel ICI checkpoints
Examples of combination therapy
Multiple ICIs
ICI and chemotherapy
ICI and radiation therapy
CD40
CAR-T cells
Vaccines
Viral vaccine immunotherapy
Conclusion
References
Chapter 19 Metabolic programming of pancreatic and colon cancer
Abstract
Keywords:
Introduction
Hypothesis
Methodology
Cell culture and cell lines
Metabolic profiling [60]
Gene expression analysis [61]
Protein expression analysis [62]
Metabolic flux analysis [63]
Functional assays [64]
In vivo studies [65]
Flow chart of methodology
Hypothetical results
Discussion
Therapeutic opportunities
Challenges and future directions
Conclusion
References
Chapter 20 Managing adverse effects of novel immunotherapies in pancreatic and colon cancers
Abstract
Keywords
Authorship contribution statement
Declaration of competing interest
Introduction
IrAEs with FDA-approved medications in colorectal cancer
Nivolumab
Pembrolizumab
Dermatological irAEs
Clinical manifestations
Workup and management
Gastrointestinal irAEs
Enterocolitis
Hepatitis
Pulmonary irAEs
Clinical manifestations
Workup and management
Endocrine irAEs
Clinical manifestation
ICI-induced hypothyroidism workup, grading, and management
ICI-induced hyperthyroidism workup, grading, and management
ICI-induced adrenal insufficiency workup, grading, and management
ICI-induced pituitary dysfunction workup, grading, and management
ICI-related diabetes mellitus workup, grading, and management
Cardiovascular irAEs
Clinical manifestations
Workup and management
Conclusions and future directions
References
Chapter 21 Expanding role of immunotherapeutics in colon and pancreatic cancers and managing their adverse effects
Abstract
Keywords
Introduction
General approach to the management of immunotherapy-related adverse events
Managing dermatological adverse effects of immunotherapy
Maculopapular rash and inflammatory dermatoses
Bullous dermatoses
Severe cutaneous adverse reaction/SJS or TEN
Management of colitis secondary to immunotherapy
Immunotherapy-related hepatotoxicity and its management
Endocrinopathies secondary to immunotherapy and their management
Hyperthyroidism and hypothyroidism
Hypophysitis
Adrenal insufficiency and type 1 diabetes mellitus
Immunotherapy-related pneumonitis and its management
Management of ICPI-related rheumatologic adverse events
Rare cardiac, renal, hematologic, and ocular adverse events
Conclusion
Conflict of interest
References
Chapter 22 The role of monoclonal antibodies in the treatment of pancreatic and colon cancers
Abstract
Keywords:
Introduction
Pancreatic cancer and colon cancer overview
Immunotherapy and monoclonal antibodies
The promise of monoclonal antibodies
Customization for targeted treatment
Mechanisms of action
Applications in pancreatic and colon cancers
Understanding monoclonal antibodies
Definition
Production process
Diverse applications
Mechanism of action
Recognizing unique proteins and antigens
Blocking growth signals
Inducing immune responses
Delivering therapeutic agents
Modulating the tumor microenvironment
Commonly used mAbs
Cetuximab (Erbitux)
Bevacizumab (Avastin)
Trastuzumab (Herceptin)
Clinical decisions and personalized medicine approach
Role of monoclonal antibodies in pancreatic cancer treatment
Targeting tumor antigens
Inhibition of signaling pathways
Immunomodulation
Drug delivery
Mechanisms of action in pancreatic cancer
Role of monoclonal antibodies in colon cancer treatment
Mechanisms of action in colon cancer
Challenges and future directions
Limited response in some patients
Optimal combination therapies
Biomarker discovery
Overcoming tumor microenvironment challenges
Immunotherapy resistance
Conclusion
References
Chapter 23 Expanding roles of microRNAs in colorectal cancer in the era of immunotherapy
Abstract
Keywords:
Conflicts of interest
Introduction/background
Structural and functional properties of miRNAs
Biogenesis of miRNA
miRNA involvement in tumorigenesis
Mechanism of miR-20a in colorectal cancer
miRNAs in colorectal cancer diagnosis/prognosis
miRNAs in the treatment response prediction of colorectal cancer
miR-20a is differentially expressed before and after chemotherapy
miR-20a as a marker for prediction/improvement of chemotherapy resistance in CRC
Potential for miRNAs as a therapeutic target
Conclusions and future perspectives
References
Chapter 24 Machine learning approaches for colorectal cancer risk prediction and stratification
Abstract
Keywords
Conflict of interest
Introduction
ML approaches and their application in CRC risk prediction and stratification
Supervised learning
Unsupervised learning
Reinforcement learning
Limitations and future perspectives
Conclusion
References
Chapter 25 Immune checkpoint inhibitors-associated cardiovascular toxicity in cancer therapy
Abstract
Keywords
Disclosure
Introduction
Clinical presentation of ICI-related cardiotoxicity
Myocarditis
Pericarditis
Myocardial infarction
Arrhythmia and conduction defects
Patient surveillance of ICIs-related cardiotoxicity
Before initiation of ICI therapy
During ICI therapy
Upon cessation of ICI in the setting of suspected myocarditis
Case presentation
Conclusion and future directions
References
Chapter 26 Lifestyle, nutrition, and risk of pancreatic and colon cancers
Abstract
Keywords:
Disclosure
Introduction/background
Pancreatic cancer
Modifiable risk factors
Nonmodifiable risk factors
Others factors
Colon cancers
Nonmodifiable risk factors
Modifiable risk factors
Medications as a risk factor
Conclusion
References
Index

Ganji Purnachandra Nagaraju

Dr. Nagaraju obtained his MSc and his PhD, both in Biotechnology, from Sri Venkateswara University in Tirupati, Andhra Pradesh, India. He received his DSc from Berhampur University in Berhampur, Odisha, India. Dr. Nagaraju’s research focuses on translational projects related to gastrointestinal malignancies. He has published over 100 research papers in highly reputed international journals and has presented more than 50 abstracts at various national and international conferences. Dr. Nagaraju is author and editor of several published books in Elsevier and Springer Nature. He serves as editorial board member of several internationally recognized academic journals. Dr. Nagaraju has received several international awards including FAACC. He also holds memberships with the Association of Scientists of Indian Origin in America (ASIOA), the Society for Integrative and Comparative Biology (SICB), The Science Advisory Board, The RNA Society, The American Association for Clinical Chemistry (AACC) and the American Association of Cancer Research (AACR).

Affiliations and expertise

Assistant Professor, School of Medicine, Division of Hematology and Oncology, University of Alabama, Birmingham, AL, USA

Soumya Dakshinamurthy

Dr. Soumya Dakshinamurthy is a Research Assistant at the Department of Clinical Virology, Sri Venkateswara Institute of Medical Sciences (SVIMS), Tirupati, India. She obtained her PhD in Molecular Biology, Tumour Virology and Epidemiology from the Department of Virology, Sri Venkateswara University, Tirupati, India. Her work focuses on early detection of cancer and host-pathogen interactions. She has authored several publications in highly reputed journals and two book chapters. She is member of various national / international professional societies

Affiliations and expertise

Sri Venkateswara University, India

Sarfraz Ahmad

Prof. Sarfraz Ahmad is Director of Clinical Research at Gynecologic Oncology Program of AdventHealth Cancer Institute (AHCI), Orlando, FL, USA. He earned his PhD in Biochemistry from North-Eastern Hill University, Shillong. Prof. Ahmad’s research focus is on the analyses of clinico-pathologic and surgical outcomes of oncology, hematology, and gastroenterology patients and to better understand the cellular/molecular mechanisms of cancer and related thromboembolic/hematologic disorders. Prof. Ahmad has published over 275 peer-reviewed scholarly research articles and book chapters, and over 400 scientific abstracts. He is a reviewer and has editorial responsibilities for several biomedical journals and books; and has received competitive research grants and national/international awards for his research contributions/accomplishments

Affiliations and expertise

AdventHealth Cancer Institute, Orlando, FL, United States

Life Sciences

Physical Sciences & Engineering

Social Sciences & Humanities

Health

Immune Therapy for Pancreatic and Colon Cancers

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Ganji Purnachandra Nagaraju

Soumya Dakshinamurthy

Sarfraz Ahmad

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