scholarly journals CD73-Generated Adenosine: Orchestrating the Tumor-Stroma Interplay to Promote Cancer Growth

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Bertrand Allard ◽  
Martin Turcotte ◽  
John Stagg
Keyword(s):  
Cancer Immunotherapy ◽  
Cancer Progression ◽  
Immune Escape ◽  
Coming Of Age ◽  
Tumor Stroma ◽  
Extracellular Adenosine ◽  
Important Barrier ◽  
Clinical Benefits ◽  
Therapeutic Opportunity

Despite the coming of age of cancer immunotherapy, clinical benefits are still modest. An important barrier to successful cancer immunotherapy is that tumors employ a number of mechanisms to facilitate immune escape, including the production of anti-inflammatory cytokines, the recruitment of regulatory immune subsets, and the production of immunosuppressive metabolites. Significant therapeutic opportunity exists in targeting these immunosuppressive pathways. One such immunosuppressive pathway is the production of extracellular adenosine by CD73, an ectonucleotidase overexpressed in various types of cancer. We hereafter review the biology of CD73 and its role in cancer progression and metastasis. We describe the role of extracellular adenosine in promoting tumor growth through paracrine and autocrine action on tumor cells, endothelial cells, and immune cells.

Targeting the Tumor-Draining Lymph Node With Adjuvant Nanoparticles for Cancer Immunotherapy

2013 ◽  
Author(s):  
Susan N. Thomas
Keyword(s):  
Drug Delivery ◽  
Lymph Node ◽  
Cancer Immunotherapy ◽  
Cancer Progression ◽  
Targeted Delivery ◽  
Immune Escape ◽  
Material Design ◽  
Draining Lymph Node ◽  
Clinical Interest ◽  
Tumor Draining Lymph Node

Immunotherapy-based approaches for cancer treatment are of increasing clinical interest. Principles of drug delivery and the emerging field of material design for immunomodulation might hold significant promise for novel approaches in cancer immunotherapy since biomaterials engineering strategies enable enhanced delivery of immune modulatory agents to tissues and cells of the immune system1. One tissue of significant clinical interest in a cancer setting is the tumor-draining lymph node (TDLN), which participates in cancer progression by enabling both metastatic dissemination as well as tumor-induced immune escape. Hence, the TDLN represents a novel target for drug delivery schemes for cancer immunotherapy. We hypothesize that targeted delivery of adjuvants (Adjs) to the TDLN using a biomaterials-based approach might promote antitumor immunity and hinder tumor growth.

scholarly journals Advances in Tumor-Stroma Interactions: Emerging Role of Cytokine Network in Colorectal and Pancreatic Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Chiara Bazzichetto ◽  
Fabiana Conciatori ◽  
Italia Falcone ◽  
Francesco Cognetti ◽  
Michele Milella ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Progression ◽  
Cancer Progression ◽  
Epidemiological Data ◽  
Tumor Stroma ◽  
Cytokine Network ◽  
Pharmacological Response ◽  
Wide Range ◽  
Clinical Models

Cytokines are a family of soluble factors (Growth Factors (GFs), chemokines, angiogenic factors, and interferons), which regulate a wide range of mechanisms in both physiological and pathological conditions, such as tumor cell growth and progression, angiogenesis, and metastasis. In recent years, the growing interest in developing new cancer targeted therapies has been accompanied by the effort to characterize Tumor Microenvironment (TME) and Tumor-Stroma Interactions (TSI). The connection between tumor and stroma is now well established and, in the last decade, evidence from genetic, pharmacological, and epidemiological data supported the importance of microenvironment in tumor progression. However, several of the mechanisms behind TSI and their implication in tumor progression remain still unclear and it is crucial to establish their potential in determining pharmacological response. Many studies have demonstrated that cytokines network can profoundly affect TME, thus displaying potential therapeutic efficacy in both preclinical and clinical models. The goal of this review is to give an overview of the most relevant cytokines involved in colorectal and pancreatic cancer progression and their implication in drug response.

scholarly journals Pan-Cancer Analysis Shows Enrichment of Macrophages, Overexpression of Checkpoint Molecules, Inhibitory Cytokines, and Immune Exhaustion Signatures in EMT-High Tumors

2022 ◽  
Vol 11 ◽  
Author(s):  
Jayesh Kumar Tiwari ◽  
Shloka Negi ◽  
Manju Kashyap ◽  
Sheikh Nizamuddin ◽  
Amar Singh ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Immune Escape ◽  
The Cancer Genome Atlas ◽  
Mesenchymal Transition ◽  
Gene Signatures ◽  
Immune Exhaustion ◽  
Cancer Types ◽  
Tcga Dataset ◽  
Pan Cancer

Epithelial–mesenchymal transition (EMT) is a highly dynamic process that occurs under normal circumstances; however, EMT is also known to play a central role in tumor progression and metastasis. Furthermore, role of tumor immune microenvironment (TIME) in shaping anticancer immunity and inducing the EMT is also well recognized. Understanding the key features of EMT is critical for the development of effective therapeutic interventions. Given the central role of EMT in immune escape and cancer progression and treatment, we have carried out a pan-cancer TIME analysis of The Cancer Genome Atlas (TCGA) dataset in context to EMT. We have analyzed infiltration of various immune cells, expression of multiple checkpoint molecules and cytokines, and inflammatory and immune exhaustion gene signatures in 22 cancer types from TCGA dataset. A total of 16 cancer types showed a significantly increased (p < 0.001) infiltration of macrophages in EMT-high tumors (mesenchymal samples). Furthermore, out of the 17 checkpoint molecules we analyzed, 11 showed a significant overexpression (p < 0.001) in EMT-high samples of at least 10 cancer types. Analysis of cytokines showed significant enrichment of immunosuppressive cytokines—TGFB1 and IL10—in the EMT-high group of almost all cancer types. Analysis of various gene signatures showed enrichment of inflammation, exhausted CD8+ T cells, and activated stroma signatures in EMT-high tumors. In summary, our pan-cancer EMT analysis of TCGA dataset shows that the TIME of EMT-high tumors is highly immunosuppressive compared to the EMT-low (epithelial) tumors. The distinctive features of EMT-high tumors are as follows: (i) the enrichment of tumor-associated macrophages, (ii) overexpression of immune checkpoint molecules, (iii) upregulation of immune inhibitory cytokines TGFB1 and IL10, and (iv) enrichment of inflammatory and exhausted CD8+ T-cell signatures. Our study shows that TIMEs of different EMT groups differ significantly, and this would pave the way for future studies analyzing and targeting the TIME regulators for anticancer immunotherapy.

scholarly journals BTLA-HVEM Couple in Health and Diseases: Insights for Immunotherapy in Lung Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Clemence Demerlé ◽  
Laurent Gorvel ◽  
Daniel Olive
Keyword(s):  
Lung Cancer ◽  
Cancer Progression ◽  
Immune Escape ◽  
Checkpoint Inhibitors ◽  
Immune Checkpoints ◽  
Tumor Immune Escape ◽  
Promising Target ◽  
Tnf Receptor Family ◽  
Receptor Family

Lung cancer is the leading cause of cancer deaths worldwide. Immunotherapies (IT) have been rapidly approved for lung cancer treatment after the spectacular results in melanoma. Responses to the currently used checkpoint inhibitors are strikingly good especially in metastatic diseases. However, durable responses are observed in only 25% of cases. Consequently, there is an urgent need for new immunotherapy targets. Among the multiple checkpoints involved in the tumor immune escape, the BTLA-HVEM couple appears to be a promising target. BTLA (B- and T- Lymphocyte Attenuator) is a co-inhibitory receptor mainly expressed by B and T cells, repressing the activation signal transduction. BTLA shares similarities with other immune checkpoints such as PD-1 and CTLA-4 which are the targets of the currently used immunotherapies. Furthermore, BTLA expression points out terminally exhausted and dysfunctional lymphocytes, and correlates with lung cancer progression. The ligand of BTLA is HVEM (Herpes Virus Entry Mediator) which belongs to the TNF receptor family. Often described as a molecular switch, HVEM is constitutively expressed by many cells, including cells from tumor and healthy tissues. In addition, HVEM seems to be involved in tumor immuno-evasion, especially in lung tumors lacking PD-L1 expression. Here, we propose to review the role of BTLA-HVEM in immuno-escape in order to highlight its potential for designing new immunotherapies.

scholarly journals The role of cancer stromal fibroblasts in mediating the effects of tobacco-induced cancer cell growth

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zai-Zai Cao ◽  
Yin-Jie Ao ◽  
Shui-Hong Zhou
Keyword(s):  
Epithelial Cells ◽  
Cancer Progression ◽  
Tumor Stroma ◽  
Tobacco Product ◽  
Cancer Cell Growth ◽  
Stromal Fibroblasts ◽  
Tobacco Products ◽  
Long Time ◽  
Major Factors

AbstractTobacco products cause a variety of cancers, nicotine and carcinogens are two major factors to link the tobacco products and various cancers. The mechanism of tobacco inducing carcinogenesis and promoting cancer progression have been studied for a long time. However, mainstream studies just focus on the mutagenic characteristics of tobacco product and its properties to induce carcinogenesis of epithelial cells. In the past decades, people began to aware of the significant role of tumor stroma in cancer development and progression. Fibroblasts, which is associated with various cancer in all stage of disease progression, are the dominant cell type in the tumor microenvironment. While only a few studies explore the crosstalk between tobacco-induced fibroblasts and surrounding epithelial cells. Our purpose is to systematically review the effects of tobacco products on fibroblasts and further discuss how these effects affect the development of cancer cells.

Human Galectin-1 and Its Inhibitors: Privileged Target for Cancer and HIV

2019 ◽  
Vol 19 (16) ◽  
pp. 1369-1378 ◽  
Author(s):  
Narella Sridhar Goud ◽  
P.S. Lakshmi Soukya ◽  
Mahammad Ghouse ◽  
Daipule Komal ◽  
Ravi Alvala ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Viral Entry ◽  
Immune Escape ◽  
Specific Binding ◽  
Therapeutic Approaches ◽  
Therapeutic Drugs ◽  
Kinetics Of ◽  
Structural Insights ◽  
Hiv 1

Galectin 1(Gal-1), a β-galactoside binding mammalian lectin of 14KDa, is implicated in many signalling pathways, immune responses associated with cancer progression and immune disorders. Inhibition of human Gal-1 has been regarded as one of the potential therapeutic approaches for the treatment of cancer, as it plays a major role in tumour development and metastasis by modulating various biological functions viz. apoptosis, angiogenesis, migration, cell immune escape. Gal-1 is considered as a biomarker in diagnosis, prognosis and treatment condition. The overexpression of Gal-1 is well established and seen in many types of cancer progression like osteosarcoma, breast, lung, prostate, melanoma, etc. Gal-1 greatly accelerates the binding kinetics of HIV-1 to susceptible cells, leading to faster viral entry and a more robust viral replication by specific binding of CD4 cells. Hence, the Gal-1 is considered a promising molecular target for the development of new therapeutic drugs for cancer and HIV. The present review laid emphasis on structural insights and functional role of Gal-1 in the disease, current Gal-1 inhibitors and future prospects in the design of specific Gal-1 inhibitors.

scholarly journals Emerging Role of Extracellular Vesicles in Immune Regulation and Cancer Progression

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3563
Author(s):  
Sonam Mittal ◽  
Prachi Gupta ◽  
Pradeep Chaluvally-Raghavan ◽  
Sunila Pradeep
Keyword(s):  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Immune Regulation ◽  
Therapeutic Intervention ◽  
Tumor Stroma ◽  
Membrane Bound ◽  
Regulatory Functions ◽  
Extracellular Environment ◽  
Insight Into

The development of effective therapies for cancer treatment requires a better understanding of the tumor extracellular environment and a dynamic interaction between tumor cells, the cells of the immune system, and the tumor stroma. Increasing evidence suggests that extracellular vesicles play an important role in this interaction. Extracellular vesicles are nanometer-sized membrane-bound vesicles secreted by various types of cells that facilitate intracellular communication by transferring proteins, various lipids, and nucleic acids, especially miRNAs, between cells. Extracellular vesicles play discrete roles in the immune regulatory functions, such as antigen presentation, and activation or suppression of immune cells. Achieving therapeutic intervention through targeting of extracellular vesicles is a crucial area of research now. Thus, a deeper knowledge of exosome biology and the molecular mechanism of immune regulation is likely to provide significant insight into therapeutic intervention utilizing extracellular vesicles to combat this dreadful disease. This review describes the recent updates on immune regulation by extracellular vesicles in cancer progression and possible use in cancer therapy.

Role of BAG3 in cancer progression: A therapeutic opportunity

2018 ◽  
Vol 78 ◽  
pp. 85-92 ◽  
Author(s):  
Margot De Marco ◽  
Anna Basile ◽  
Vittoria Iorio ◽  
Michelina Festa ◽  
Antonia Falco ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Therapeutic Opportunity
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