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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5563_Библиотеки_им_академика_М_И_Перельмана.pdf
The Dynamics of Tumor
Microenvironment and
Therapeutic Targets
The tumor microenvironment (TME) plays a signicant role in inuencing
tumor aggressiveness and therapeutic outcomes, presenting both challenges
and opportunities in oncology. The Dynamics of Tumor Microenvironment and
Therapeutic Targets provides a detailed overview of the complex nature of the
TME, highlighting its dynamic cellular and molecular components. Each chapter
systematically examines a specic element of the TME, outlining its role in tumor
initiation, progression, dormancy, and suppression. The book discusses the use of
molecular inhibitors that disrupt tumor-promoting interactions within the TME.
Additionally, it covers immune therapies designed to reprogram immune cells in the
TME to enhance the effectiveness and durability of cancer treatments. This volume
also addresses recent advancements in therapeutic strategies targeting the TME,
including the incorporation of contemporary computational methods. Notably, the
application of articial intelligence (AI) and machine learning (ML) to TME analysis
is explored, showcasing their utility in biomarker discovery and the development of
precision oncology tools.
Key Features
• Comprehensive coverage of the cellular and noncellular components of the
TME, with an emphasis on their phenotypic and functional heterogeneity.
• Detailed discussion of both targetable and non-targetable elements of the
TME and their relevance in therapeutic development.
• A dedicated chapter on AI-/ML-based methodologies for TME proling,
reecting the emerging role of computational biology in oncology research.
• Critical descriptions of clinical trials targeting various aspects of the TME,
alongside a synthesis of relevant translational and preclinical studies.
This volume serves as a valuable resource for graduate students, early career
researchers, and established investigators in cancer biology, tumor immunology, and
translational oncology. It provides foundational knowledge as well as insights into
emerging therapeutic paradigms centered on the TME.
The Dynamics of Tumor
Microenvironment and
Therapeutic Targets
Edited by
Shyamasree Ghosh and Sanjima Pal
Designed cover image: Getty Images
First edition published 2026
by CRC Press
2385 NW Executive Center Drive, Suite 320, Boca Raton FL 33431
and by CRC Press
4 Park Square, Milton Park, Abingdon, Oxon, OX14 4RN
CRC Press is an imprint of Taylor& Francis Group, LLC
© 2026 selection and editorial matter, Shyamasree Ghosh and Sanjima Pal; individual chapters,
the contributors
Reasonable efforts have been made to publish reliable data and information, but the author and
publisher cannot assume responsibility for the validity of all materials or the consequences of
their use. The authors and publishers have attempted to trace the copyright holders of all material
reproduced in this publication and apologize to copyright holders if permission to publish in this
form has not been obtained. If any copyright material has not been acknowledged please write
and let us know so we may rectify in any future reprint.
Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, repro-
duced, transmitted, or utilized in any form by any electronic, mechanical, or other means, now
known or hereafter invented, including photocopying, microlming, and recording, or in any
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For permission to photocopy or use material electronically from this work, access www.
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Danvers, MA 01923, 978-750-8400. For works that are not available on CCC please contact
mpkbookspermissions@tandf.co.uk
Trademark notice: Product or corporate names may be trademarks or registered trademarks and
are used only for identication and explanation without intent to infringe.
ISBN: 978-1-032-52049-0 (hbk)
ISBN: 978-1-032 -52051-3 (pbk)
ISBN: 978-1-003-40502-3 (ebk)
DOI: 10.1201/9781003405023
Typeset in Times
by Apex CoVantage, LLC
v
Contents
Preface.......................................................................................................................ix
About the Editors ...................................................................................................... xi
Contributors ............................................................................................................ xiii
Chapter 1 Tumor Microenvironment: An Overview Since Its
Conceptualization ................................................................................. 1
Shyamasree Ghosh and Suchandra Chowdhury
1.1 Tumor Microenvironment (TME) ............................................. 1
1.2 TME: AJourney Through History ............................................ 1
1.3 TME Components ..................................................................... 3
1.3.1 Cells ............................................................................... 4
1.3.2 Noncellular Components ............................................. 12
1.4 Discussion ................................................................................ 15
References .......................................................................................... 15
Chapter 2 Shaping Cancer: Inuence of Immune Cell Dynamics in the
Tumor Microenvironment .................................................................. 25
Ananya Jana, Cameliya Singha Roy, and Sanjima Pal
2.1 Introduction ............................................................................. 25
2.2 Key Immune Phenomena Shaping the TIME ......................... 27
2.2.1 Phagocytosis ................................................................ 27
2.2.2 Antigen Presentation ................................................... 28
2.2.3 Cancer Immunoediting ................................................ 29
2.2.4 Cytokine-Chemokine-Complement Mediated
Networks in the TIME .................................................31
2.3 Innate Immune Networks in the TIME ................................... 33
2.4 Adaptive Immunity Networks in the TIME ............................ 36
2.5 Discussions .............................................................................. 38
References .......................................................................................... 38
Chapter 3 The Inuence of Cancer-Associated Fibroblasts in the Tumor
Microenvironment and Their Effects on Glioblastoma ..................... 48
Mirudula Elanchezhian, Ashwin Kumar Jainarayan, and Arpit
Kumar Pradhan
3.1 Introduction ............................................................................. 48
3.1.1 Denition and Overview of Cancer-Associated
Fibroblasts ................................................................... 48
vi Contents
3.1.2 Importance of Studying CAFs in
Cancer Research .......................................................... 49
3.2 Origin of CAFs ........................................................................ 50
3.3 CAF Biomarkers .......................................................................51
3.3.1 Cancer-Promoting CAF Biomarkers ............................52
3.3.2 Cancer-Restraining CAF Biomarkers ..........................55
3.3.3 CAF Biomarkers with a Dual Role...............................55
3.3.4 Other CAF Markers with Unclear Functions .............. 56
3.4 Heterogeneity and Plasticity of CAFs ..................................... 57
3.4.1 Molecular Mechanisms Regulating CAF
Heterogeneity ............................................................... 57
3.4.2 Functional Heterogeneity of CAFs .............................. 58
3.5 Tumor Microenvironment in Glioblastoma ............................. 60
3.6 Cancer-Associated Fibroblasts in Glioblastoma ....................... 61
3.7 Therapeutic Targeting of CAFs ............................................... 62
References .......................................................................................... 63
Chapter 4 Redening the Role of Endothelial Cells in the Tumor
Microenvironment ...............................................................................81
Suchandra Chowdhury and Sanjima Pal
4.1 Introduction ..............................................................................81
4.2 Endothelial Cells (ECs) ............................................................81
4.3 Tumor Endothelial Cells (TECs) ............................................. 82
4.4 Heterogeneity of TECs ............................................................ 83
4.5 Modulation of TEC Characteristics by the TME .................... 84
4.6 Immunomodulatory Endothelial Cells .................................... 84
4.7 Role of Tumor Endothelial Cells in Angiogenesis .................. 86
4.8 Endothelial Cells in Cancer Therapy ...................................... 86
4.9 Discussion ................................................................................ 87
References .......................................................................................... 88
Chapter 5 Therapeutic Interventions in Modulating Tumor
Microenvironment ...............................................................................91
Debasis Bisoi and Lopamudra Das
5.1 Introduction ..............................................................................91
5.2 TME Therapies ........................................................................ 92
5.2.1 Tumor-Associated Immune Cells ................................ 92
5.2.2 Therapies Directed Toward the Tumor-Associated
Vasculature .................................................................. 99
5.2.3 Therapies Directed Against Extracellular Matrix
and Tumor Stroma ......................................................101
5.3 Discussion ...............................................................................102
References ........................................................................................ 104
Contents vii
Chapter 6 Drug Repurposing and Tumor Microenvironment in Cancer ����������� 115
Waliza Ansar
6�1 Introduction ����������������������������������������������������������������������������115
6�2 Cancer and the TME: AWeb of Interactions ������������������������� 117
6�3 Cancer and Traditional Drug ��������������������������������������������������119
6�4 Drug Repurposing ����������������������������������������������������������������� 120
6�5 The TME and Drug Repurposing ������������������������������������������121
6�6 Drug Repurposing in Cancer �������������������������������������������������� 121
6�7 Discussion ������������������������������������������������������������������������������ 125
References ���������������������������������������������������������������������������������������� 125
Chapter 7 Tumor Microenvironment and Cancer Growth, Detection Using
AI, and Computer Vision Techniques �����������������������������������������������129
Rathi Dasgupta
7�1 The Dynamic Ecosystem of the Tumor
Microenvironment ������������������������������������������������������������������129
7�2 Cellular Components ��������������������������������������������������������������129
7�3 Noncellular Components ��������������������������������������������������������130
7�4 TME-Driven Support of Cancer Hallmarks���������������������������130
7�4�1 The TME Confers Resistance to Apoptosis
Through Multiple Mechanisms ����������������������������������131
7�4�2 Inducing Angiogenesis, Formation of New Blood
Vessels Is a Critical TME-Dependent Process ����������� 131
7�4�3 Immunomodulation in the TME ��������������������������������131
7�4�4 The TME in Therapeutic Response and
Resistance �������������������������������������������������������������������132
7�5 Metabolic Reprogramming in the TME ���������������������������������132
7�6 Therapeutic Targeting of the TME �����������������������������������������133
7�7 Articial Intelligence and Machine Learning ������������������������133
7�8 Direction of Future Research in AI ����������������������������������������135
7�9 Articial Intelligence and Machine Learning in TME
Analysis and Detection �����������������������������������������������������������136
7�9�1 Digital Pathology and Computer Vision���������������������137
7�9�2 Multi-Omics Integration ���������������������������������������������137
7�9�3 Predictive Modeling of TME Features �����������������������137
7�9�4 Clinical Applications of AI/ML for the TME ������������138
7�9�5 Emerging Frontiers in AI/ML for TME Analysis ������138
7�10 Balancing Model Complexity with Interpretability for
Clinical Implementation ���������������������������������������������������������139
7�11 Spatial Transcriptomics and Proteomics Mapping the
Geographic Organization of the TME �����������������������������������139
References ���������������������������������������������������������������������������������������� 139
Index ����������������������������������������������������������������������������������������������������������������������� 143
ix
Preface
Tumor microenvironment (TME) is a dynamic ecosystem surrounding the tumor
cells and regularly being considered as one of the major determinants of tumor evo-
lution, proliferation, metastasis, and therapy resistance. Non-malignant components
surrounding tumor cells include an array of specialized endothelial cells, broblasts,
immune cells, and noncellular agents, such as cytokines, chemokines, growth fac-
tors, soluble tumor antigens, circulating nucleic acids, extracellular matrix (ECM)
comprising collagen, laminin, bronectin, hyaluronan, and so on are responsible of
constructing the TME. The TME ecosystem continuously exhibits remodeling and
further elevate tumor heterogeneity.
The molecular mechanisms and stimuli driving tumor initiation and progression
differ signicantly from those in normal physiological conditions. Every component
of the TME plays a crucial role in activating signaling factors that facilitate the tran-
sition from normal tissue to a benign state and eventually to a malignant tumor. The
nature of the TME differs based on the types of cancer or organ on which tumor is
developed. Each patient displays a highly heterogenous TME. Treatment sensitiv-
ity of the tumors not only depends on their capacity to clonally evolve as resistant
tumor cells but also the activities of cellular components of the TME. Phenotypic
and functional evaluation of the TME is very important for better understanding of
heterogenous tumor behavior and therapy response. Molecularly targeted therapies
can reverse the polarization of protumor cellular TME components into antitumor
conditions.
Orchestrated functions of all these non-malignant components and tumor cells
are pivotal to the TME, promoting immune suppression, tumorigenesis, resistance to
drug delivery, metabolic adaptation, signaling associated with intrinsic and adaptive
therapy resistance, and metastasis. Therefore, in-depth understanding of the dynam-
ics of TME components is the need of the hour. This book has discussed the func-
tional and regulatory roles of a few critical cellular and noncellular components in
modulation of the TME and concomitant heterogeneity, as well as potential to polar-
ize into antitumor state after therapeutic interventions.
Shyamasree and Sanjima