scholarly journals Cancer-associated fibroblasts and their influence on tumor immunity and immunotherapy

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Richard Lee Barrett ◽  
Ellen Puré
Keyword(s):  
Solid Tumors ◽  
Immune Cells ◽  
Antitumor Immunity ◽  
Critical Role ◽  
Therapeutic Resistance ◽  
Cancer Associated Fibroblasts ◽  
Tissue Architecture ◽  
Immunosuppressive Activity ◽  
Major Mechanism ◽  
And Function

Fibroblasts play an essential role in organogenesis and the integrity of tissue architecture and function. Growth in most solid tumors is dependent upon remodeling ‘stroma’, composed of cancer-associated fibroblasts (CAFs) and extracellular matrix (ECM), which plays a critical role in tumor initiation, progression, metastasis, and therapeutic resistance. Recent studies have clearly established that the potent immunosuppressive activity of stroma is a major mechanism by which stroma can promote tumor progression and confer resistance to immune-based therapies. Herein, we review recent advances in identifying the stroma-dependent mechanisms that regulate cancer-associated inflammation and antitumor immunity, in particular, the interactions between fibroblasts and immune cells. We also review the potential mechanisms by which stroma can confer resistance to immune-based therapies for solid tumors and current advancements in stroma-targeted therapies.

scholarly journals Cancer-Associated Fibroblasts: Understanding Their Heterogeneity

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3108
Author(s):  
Kévin Louault ◽  
Rong-Rong Li ◽  
Yves A. DeClerck
Keyword(s):  
Cancer Progression ◽  
Immune Cell ◽  
Critical Role ◽  
Cell Reprogramming ◽  
Therapeutic Resistance ◽  
Cancer Associated Fibroblasts ◽  
Specific Function ◽  
Multiple Components ◽  
Extracellular Matrix Molecules ◽  
Heterogeneous Nature

The tumor microenvironment (TME) plays a critical role in tumor progression. Among its multiple components are cancer-associated fibroblasts (CAFs) that are the main suppliers of extracellular matrix molecules and important contributors to inflammation. As a source of growth factors, cytokines, chemokines and other regulatory molecules, they participate in cancer progression, metastasis, angiogenesis, immune cell reprogramming and therapeutic resistance. Nevertheless, their role is not fully understood, and is sometimes controversial due to their heterogeneity. CAFs are heterogeneous in their origin, phenotype, function and presence within tumors. As a result, strategies to target CAFs in cancer therapy have been hampered by the difficulties in better defining the various populations of CAFs and by the lack of clear recognition of their specific function in cancer progression. This review discusses how a greater understanding of the heterogeneous nature of CAFs could lead to better approaches aimed at their use or at their targeting in the treatment of cancer.

scholarly journals Crosstalk between cancer-associated fibroblasts and immune cells in the tumor microenvironment: new findings and future perspectives

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiaoqi Mao ◽  
Jin Xu ◽  
Wei Wang ◽  
Chen Liang ◽  
Jie Hua ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Immune Cells ◽  
Immune Cell ◽  
Critical Role ◽  
Cancer Associated Fibroblasts ◽  
Cell Of Origin ◽  
Future Perspectives ◽  
Immune Microenvironment ◽  
New Findings ◽  
Essential Components

AbstractCancer-associated fibroblasts (CAFs), a stromal cell population with cell-of-origin, phenotypic and functional heterogeneity, are the most essential components of the tumor microenvironment (TME). Through multiple pathways, activated CAFs can promote tumor growth, angiogenesis, invasion and metastasis, along with extracellular matrix (ECM) remodeling and even chemoresistance. Numerous previous studies have confirmed the critical role of the interaction between CAFs and tumor cells in tumorigenesis and development. However, recently, the mutual effects of CAFs and the tumor immune microenvironment (TIME) have been identified as another key factor in promoting tumor progression. The TIME mainly consists of distinct immune cell populations in tumor islets and is highly associated with the antitumor immunological state in the TME. CAFs interact with tumor-infiltrating immune cells as well as other immune components within the TIME via the secretion of various cytokines, growth factors, chemokines, exosomes and other effector molecules, consequently shaping an immunosuppressive TME that enables cancer cells to evade surveillance of the immune system. In-depth studies of CAFs and immune microenvironment interactions, particularly the complicated mechanisms connecting CAFs with immune cells, might provide novel strategies for subsequent targeted immunotherapies. Herein, we shed light on recent advances regarding the direct and indirect crosstalk between CAFs and infiltrating immune cells and further summarize the possible immunoinhibitory mechanisms induced by CAFs in the TME. In addition, we present current related CAF-targeting immunotherapies and briefly describe some future perspectives on CAF research in the end.

scholarly journals Emerging concepts and future challenges in innate lymphoid cell biology

2016 ◽  
Vol 213 (11) ◽  
pp. 2229-2248 ◽  
Author(s):  
Elia D. Tait Wojno ◽  
David Artis
Keyword(s):  
Immune Cells ◽  
Cell Biology ◽  
Critical Role ◽  
Cell Types ◽  
Lymphoid Cells ◽  
Adaptive Immune Cells ◽  
New Findings ◽  
Basic Studies ◽  
New Treatments ◽  
And Function

Innate lymphoid cells (ILCs) are innate immune cells that are ubiquitously distributed in lymphoid and nonlymphoid tissues and enriched at mucosal and barrier surfaces. Three major ILC subsets are recognized in mice and humans. Each of these subsets interacts with innate and adaptive immune cells and integrates cues from the epithelium, the microbiota, and pathogens to regulate inflammation, immunity, tissue repair, and metabolic homeostasis. Although intense study has elucidated many aspects of ILC development, phenotype, and function, numerous challenges remain in the field of ILC biology. In particular, recent work has highlighted key new questions regarding how these cells communicate with their environment and other cell types during health and disease. This review summarizes new findings in this rapidly developing field that showcase the critical role ILCs play in directing immune responses through their ability to interact with a variety of hematopoietic and nonhematopoietic cells. In addition, we define remaining challenges and emerging questions facing the field. Finally, this review discusses the potential application of basic studies of ILC biology to the development of new treatments for human patients with inflammatory and infectious diseases in which ILCs play a role.

scholarly journals Immunometabolism in the Tumor Microenvironment

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Dominic G. Roy ◽  
Irem Kaymak ◽  
Kelsey S. Williams ◽  
Eric H. Ma ◽  
Russell G. Jones
Keyword(s):  
Tumor Microenvironment ◽  
Immune Cells ◽  
Cancer Biology ◽  
Antitumor Immunity ◽  
Immune Cell ◽  
Metabolic Reprogramming ◽  
Proper Function ◽  
Annual Review ◽  
Publication Date ◽  
And Function

Advances in immunotherapy have underscored the importance of antitumor immune responses in controlling cancer. However, the tumor microenvironment (TME) imposes several obstacles to the proper function of immune cells, including a metabolically challenging and immunosuppressive microenvironment. The increased metabolic activity of tumor cells can lead to the depletion of key nutrients required by immune cells and the accumulation of byproducts that hamper antitumor immunity. Furthermore, the presence of suppressive immune cells, such as regulatory T cells and myeloid-derived suppressor cells, and the expression of immune inhibitory receptors can negatively impact immune cell metabolism and function. This review summarizes the metabolic reprogramming that is characteristic of various immune cell subsets, discusses how the metabolism and function of immune cells is shaped by the TME, and highlights how therapeutic interventions aimed at improving the metabolic fitness of immune cells and alleviating the metabolic constraints in the TME can boost antitumor immunity. Expected final online publication date for the Annual Review of Cancer Biology, Volume 5 is March 4, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Interleukin-34 promotes tumorigenic signals for colon cancer cells

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Eleonora Franzè ◽  
Irene Marafini ◽  
Edoardo Troncone ◽  
Silvia Salvatori ◽  
Giovanni Monteleone
Keyword(s):  
Cancer Cells ◽  
Immune Cells ◽  
Stromal Cells ◽  
Colon Carcinogenesis ◽  
Cell Types ◽  
Western World ◽  
Cancer Associated Fibroblasts ◽  
Colon Cancer Cells ◽  
Growth And Survival ◽  
And Function

AbstractColorectal carcinoma (CRC) is one of the most common forms of malignancy in the Western world. Accumulating evidence indicates that colon carcinogenesis is tightly controlled by tumour-associated immune cells and stromal cells, which can either stimulate or suppress CRC cell growth and survival, mainly via the production of cytokines. Interleukin-34 (IL-34), a cytokine known to regulate mainly monocyte/macrophage survival and function, is highly produced within the CRC microenvironment by several cell types, including cancer cells, tumour-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs), and regulates the pro-tumoural functions of such cells. In this article, we summarize the available data supporting the multiple effects of IL-34 in human CRC.

scholarly journals Harnessing tumor-associated macrophages as aids for cancer immunotherapy

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Xiaolei Li ◽  
Rui Liu ◽  
Xiao Su ◽  
Yongsha Pan ◽  
Xiaofeng Han ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Immune Cells ◽  
Antitumor Immunity ◽  
Therapeutic Strategies ◽  
Therapeutic Approaches ◽  
Tumor Associated Macrophages ◽  
Therapeutic Modalities ◽  
Preclinical And Clinical Studies ◽  
Tumor Types ◽  
Cancer Immunotherapies

AbstractCancer immunotherapies that engage immune cells to fight against tumors are proving to be powerful weapons in combating cancer and are becoming increasingly utilized in the clinics. However, for the majority of patients with solid tumors, little or no progress has been seen, presumably due to lack of adequate approaches that can reprogram the local immunosuppressive tumor milieu and thus reinvigorate antitumor immunity. Tumor-associated macrophages (TAMs), which abundantly infiltrate most solid tumors, could contribute to tumor progression by stimulating proliferation, angiogenesis, metastasis, and by providing a barrier against antitumor immunity. Initial TAMs-targeting strategies have shown efficacy across therapeutic modalities and tumor types in both preclinical and clinical studies. TAMs-targeted therapeutic approaches can be roughly divided into those that deplete TAMs and those that modulate TAMs activities. We here reviewed the mechanisms by which macrophages become immunosuppressive and compromise antitumor immunity. TAMs-focused therapeutic strategies are also summarized.

scholarly journals The Tumor Microenvironment in Neuroblastoma: New Players, New Mechanisms of Interaction and New Perspectives

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2912 ◽  
Author(s):  
Laurence Blavier ◽  
Ren-Ming Yang ◽  
Yves A. DeClerck
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Inflammatory Cells ◽  
Therapeutic Strategies ◽  
Complex Nature ◽  
Cancer Associated Fibroblasts ◽  
Immunosuppressive Activity ◽  
And Function ◽  
The Impact ◽  
Initial Focus

The contribution of the tumor microenvironment (TME) to cancer progression has been well recognized in recent decades. As cancer therapeutic strategies are increasingly precise and include immunotherapies, knowledge of the nature and function of the TME in a tumor becomes essential. Our understanding of the TME in neuroblastoma (NB), the second most common solid tumor in children, has significantly progressed from an initial focus on its Schwannian component to a better awareness of its complex nature, which includes not only immune but also non-immune cells such as cancer-associated fibroblasts (CAFs), the contribution of which to inflammation and interaction with tumor-associated macrophages (TAMs) is now recognized. Recent studies on the TME landscape of NB tumors also suggest significant differences between MYCN-amplified (MYCN-A) and non-amplified (MYCN-NA) tumors, in their content in stromal and inflammatory cells and their immunosuppressive activity. Extracellular vesicles (EVs) released by cells in the TME and microRNAs (miRs) present in their cargo could play important roles in the communication between NB cells and the TME. This review article discusses these new aspects of the TME in NB and the impact that information on the TME landscape in NB will have in the design of precise, biomarker-integrated clinical trials.

The Laryngeal Epithelium in Reflux

2011 ◽  
Vol 21 (3) ◽  
pp. 112-117 ◽  
Author(s):  
Elizabeth Erickson-Levendoski ◽  
Mahalakshmi Sivasankar
Keyword(s):  
Laryngopharyngeal Reflux ◽  
Critical Role ◽  
Structure And Function ◽  
Laryngeal Disease ◽  
Health And Disease ◽  
And Function ◽  
The Impact

The epithelium plays a critical role in the maintenance of laryngeal health. This is evident in that laryngeal disease may result when the integrity of the epithelium is compromised by insults such as laryngopharyngeal reflux. In this article, we will review the structure and function of the laryngeal epithelium and summarize the impact of laryngopharyngeal reflux on the epithelium. Research investigating the ramifications of reflux on the epithelium has improved our understanding of laryngeal disease associated with laryngopharyngeal reflux. It further highlights the need for continued research on the laryngeal epithelium in health and disease.

Adoptive Cell Therapy for Gastrointestinal Cancers

2020 ◽  
Vol 04 (04) ◽  
pp. 345-350
Author(s):  
Ryan J. Slovak ◽  
Hyun S. Kim
Keyword(s):  
Cell Therapy ◽  
Clinical Research ◽  
Solid Tumors ◽  
Immune Cells ◽  
Ex Vivo ◽  
Adoptive Cell Therapy ◽  
Hematologic Malignancies ◽  
Gastrointestinal Cancers ◽  
Gastrointestinal Malignancies ◽  
Specific Antigens

AbstractThe reinfusion of autologous or allogeneic immune cells that have been educated and/or engineered ex vivo to respond to tumor-specific antigens is termed “adoptive cell therapy.” While adoptive cell therapy has made tremendous strides in the treatment of hematologic malignancies, its utilization for solid tumors has lagged somewhat behind. The purpose of this article is to concisely review the clinical research that has been done to investigate adoptive cell therapy as a treatment for gastrointestinal malignancies.

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