scholarly journals The role of the tumour microenvironment in immunotherapy

2017 ◽  
Vol 24 (12) ◽  
pp. T283-T295 ◽  
Author(s):  
Stephan Gasser ◽  
Lina H K Lim ◽  
Florence S G Cheung
Keyword(s):  
Current Knowledge ◽  
Tumour Progression ◽  
Tumour Microenvironment ◽  
Tumour Immunity ◽  
Recent Success ◽  
Cytokines And Chemokines ◽  
Solid Malignancies ◽  
Variable Success ◽  
Molecular Patterns

Recent success in immunomodulating strategies in lung cancer and melanoma has prompted much enthusiasm in their potential to treat other advanced solid malignancies. However, their applications have shown variable success and are even ineffective against some tumours. The efficiency of immunotherapies relies on an immunogenic tumour microenvironment. The current field of cancer immunology has focused on understanding the interaction of cancer and host immune cells to break the state of immune tolerance and explain how molecular patterns of cytokines and chemokines affect tumour progression. Here, we review our current knowledge of how inherent properties of tumours and their different tumour microenvironments affect therapeutic outcome. We also discuss insights into recent multimodal therapeutic approaches that target tumour immune evasion and suppression to restore anti-tumour immunity.

scholarly journals EVs as Potential New Therapeutic Tool/Target in Gastrointestinal Cancer and HCC

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3019
Author(s):  
Artur Słomka ◽  
Tudor Mocan ◽  
Bingduo Wang ◽  
Iuliana Nenu ◽  
Sabine Urban ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Tumour Progression ◽  
Cell Communication ◽  
Tumour Microenvironment ◽  
Host Immune System ◽  
Mediated Communication ◽  
Cell Content ◽  
Cytokines And Chemokines ◽  
Liver Cancers ◽  
Cancer Types

For more than a decade, extracellular vesicles (EVs) have been in focus of science. Once thought to be an efficient way to eliminate undesirable cell content, EVs are now well-accepted as being an important alternative to cytokines and chemokines in cell-to-cell communication route. With their cargos, mainly consisting of functional proteins, lipids and nucleic acids, they can activate signalling cascades and thus change the phenotype of recipient cells at local and systemic levels. Their substantial role as modulators of various physiological and pathological processes is acknowledged. Importantly, more and more evidence arises that EVs play a pivotal role in many stages of carcinogenesis. Via EV-mediated communication, tumour cells can manipulate cells from host immune system or from the tumour microenvironment, and, ultimately, they promote tumour progression and modulate host immunity towards tumour’s favour. Additionally, the role of EVs in modulating resistance to pharmacological and radiological therapy of many cancer types has become evident lately. Our understanding of EV biology and their role in cancer promotion and drug resistance has evolved considerably in recent years. In this review, we specifically discuss the current knowledge on the association between EVs and gastrointestinal (GI) and liver cancers, including their potential for diagnosis and treatment.

scholarly journals The Yin and Yang of tumour-derived extracellular vesicles in tumour immunity

2020 ◽  
Author(s):  
Takayoshi Yamauchi ◽  
Toshiro Moroishi
Keyword(s):  
Extracellular Vesicles ◽  
Tumour Progression ◽  
Tumour Microenvironment ◽  
Host Immunity ◽  
Biological Processes ◽  
Small Particles ◽  
Tumour Immunity ◽  
Heterogeneous Nature ◽  
Yin And Yang ◽  
Cellular Components

Abstract Extracellular vesicles (EVs) are small particles that are naturally released from various types of cells. EVs contain a wide variety of cellular components, such as proteins, nucleic acids, lipids and metabolites, which facilitate intercellular communication in diverse biological processes. In the tumour microenvironment, EVs have been shown to play important roles in tumour progression, including immune system–tumour interactions. Although previous studies have convincingly demonstrated the immunosuppressive functions of tumour-derived EVs, some studies have suggested that tumour-derived EVs can also stimulate host immunity, especially in therapeutic conditions. Recent studies have revealed the heterogeneous nature of EVs with different structural and biological characteristics that may account for the divergent functions of EVs in tumour immunity. In this review article, we provide a brief summary of our current understanding of tumour-derived EVs in immune activation and inhibition. We also highlight the emerging utility of EVs in the diagnosis and treatment of cancers and discuss the potential clinical applications of tumour-derived EVs.

scholarly journals Hypoxia and proangiogenic proteins in human ameloblastoma

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Raíssa Pinheiro de Mendonça ◽  
Karolyny Martins Balbinot ◽  
Beatriz Voss Martins ◽  
Maria Sueli da Silva Kataoka ◽  
Ricardo Alves Mesquita ◽  
...  
Keyword(s):  
Aggressive Behaviour ◽  
Tumour Progression ◽  
Tumour Microenvironment ◽  
Odontogenic Cysts ◽  
Biological Behaviour ◽  
Odontogenic Tumours ◽  
Anti Vegf ◽  
The Mean

Abstract Ameloblastomas are epithelial odontogenic tumours that, although benign, are locally invasive and may exhibit aggressive behaviour. In the tumour microenvironment, the concentration of oxygen is reduced, which leads to intratumoral hypoxia. Under hypoxia, the crosstalk between the HIF-1α, MMP-2, VEGF, and VEGFR-2 proteins has been associated with hypoxia-induced angiogenesis, leading to tumour progression and increased invasiveness. This work showcases 24 ameloblastoma cases, 10 calcifying odontogenic cysts, and 9 dental follicles, used to investigate the expression of these proteins by immunohistochemistry. The anti-HIF-1α, anti-MMP-2, anti-VEGF, and anti-VEGFR-2 primary antibodies are used in this work. The results have been expressed by the mean grey value after immunostaining in images acquired with an objective of 40×. The ameloblastoma samples showed higher immunoexpression of HIF-1α, MMP-2, VEGF, and VEGFR-2 when compared to the dental follicles and calcifying odontogenic cysts. Ameloblastomas show a higher degree of expression of proteins associated with intratumoral hypoxia and proangiogenic proteins, which indicates the possible role of these proteins in the biological behaviour of this tumour.

scholarly journals Satellitosis, a Crosstalk between Neurons, Vascular Structures and Neoplastic Cells in Brain Tumours; Early Manifestation of Invasive Behaviour

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3720
Author(s):  
Prospero Civita ◽  
Ortenzi Valerio ◽  
Antonio Giuseppe Naccarato ◽  
Mark Gumbleton ◽  
Geoffrey J. Pilkington
Keyword(s):  
Brain Tumours ◽  
Current Knowledge ◽  
Glioma Cells ◽  
Tumour Microenvironment ◽  
High Grade ◽  
Critical Knowledge ◽  
Glioma Growth ◽  
Vascular Structures ◽  
Early Manifestation

The secondary structures of Scherer commonly known as perineuronal and perivascular satellitosis have been identified as a histopathological hallmark of diffuse, invasive, high-grade gliomas. They are recognised as perineuronal satellitosis when clusters of neoplastic glial cells surround neurons cell bodies and perivascular satellitosis when such tumour cells surround blood vessels infiltrating Virchow–Robin spaces. In this review, we provide an overview of emerging knowledge regarding how interactions between neurons and glioma cells can modulate tumour evolution and how neurons play a key role in glioma growth and progression, as well as the role of perivascular satellitosis into mechanisms of glioma cells spread. At the same time, we review the current knowledge about the role of perineuronal satellitosis and perivascular satellitosis within the tumour microenvironment (TME), in order to highlight critical knowledge gaps in research space.

scholarly journals Toll-Like Receptor 3 in Solid Cancer and Therapy Resistance

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3227
Author(s):  
Ximena Maria Muresan ◽  
Jan Bouchal ◽  
Zoran Culig ◽  
Karel Souček
Keyword(s):  
Tumor Regression ◽  
Current Knowledge ◽  
Therapy Resistance ◽  
Solid Cancer ◽  
Type I ◽  
Toll Like Receptor ◽  
Cytokines And Chemokines ◽  
Antiviral Function ◽  
Antigen Presenting

Toll-like receptor 3 (TLR3) is a member of the TLR family, which has been extensively studied for its antiviral function. It is highly expressed in the endosomes of antigen-presenting immune cells and epithelial cells. TLR3 binds specifically double-strand RNAs (dsRNAs), leading to the activation of mainly two downstream pathways: the phosphorylation of IRF3, with subsequent production of type I interferon, and the activation of NF-κB, which drives the production of inflammatory cytokines and chemokines. Several studies have demonstrated TLR3 expression in multiple neoplasia types including breast, prostate, and lung cancer. Most studies were focused on the beneficial role of TLR3 activation in tumor cells, which leads to the production of cytotoxic cytokines and interferons and promotes caspase-dependent apoptosis. Indeed, ligands of this receptor were proposed for the treatment of cancer, also in combination with conventional chemotherapy. In contrast to these findings, recent evidence showed a link between TLR3 and tumor progression, metastasis, and therapy resistance. In the present review, we summarize the current knowledge of the mechanisms through which TLR3 can either lead to tumor regression or promote carcinogenesis as well as the potential of TLR-based therapies in resistant cancer.

Stem Cells in Tumour Microenvironment Aid in Prolonged Survival Rate of Cancer Cells and Developed Drug Resistance: Major Challenge in Osteosarcoma Treatment

2020 ◽  
Vol 21 (1) ◽  
pp. 44-52
Author(s):  
Bhaskar Birru ◽  
ChandraSai Potla Durthi ◽  
Santhosh Kacham ◽  
Madhuri Pola ◽  
Satish Babu Rajulapati ◽  
...  
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Tumour Progression ◽  
Combined Treatment ◽  
Bone Cancer ◽  
Tumour Microenvironment ◽  
Surgical Removal ◽  
Therapeutic Approaches ◽  
Hypoxic Environment

Osteosarcoma is an aggressive bone cancer found in children and adolescents. The combined treatment strategy includes the surgical removal of tumour and subsequent chemotherapy to prevent the reoccurrence has been a widely accepted approach. However, the drug resistance developed by tumour cells causes recurrence of cancer. It is imperative to understand the molecular mechanism involved in the development of drug resistance and tumour progression for developing potential therapy. Tumour microenvironment and cellular cross-talk via activation of various signalling pathways are responsible for tumour progression and metastasis. The comprehensive reviews are already available on the tumour microenvironment, signalling cascades responsible for tumour progression, and cellular crosstalk between malignant cells and immune cells. Therefore, we intend to provide comprehend review postulating the importance of mesenchymal stem cells (MSCs) in osteosarcoma progression and metastasis. This paper is aimed to provide information sequentially includes: tumour microenvironment, MSCs role in osteosarcoma progression, the hypoxic environment in MSCs recruitment at the tumour site and the importance of exosomes in tumorigenesis, progression and metastasis. Overall, this review may enlighten the research on the role of MSCs and MSCs derived exosome in osteosarcoma progression and drug resistance. This possibly may result in developing novel therapeutic approaches to combat the osteosarcoma effectively and contributes for the development of prognosis tools for early diagnosis.

Clinical efficacy of immune checkpoint inhibitors in patients with brain metastases

Immunotherapy ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 419-432
Author(s):  
Vincenzo Di Nunno ◽  
Giacomo Nuvola ◽  
Mirta Mosca ◽  
Ilaria Maggio ◽  
Lidia Gatto ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Standard Treatment ◽  
Current Knowledge ◽  
Checkpoint Inhibitors ◽  
Clinical Role ◽  
Negative Prognostic Factor ◽  
Solid Malignancies

Brain metastases (BMs) represent a negative prognostic factor for patients with solid malignancies. BMs are generally approached with loco-regional treatments and the blood–brain barrier limits the efficacy of some systemic drugs. The aim of this review is to summarize current knowledge about the role of immune checkpoint inhibitors for the management of brain metastases in patients with solid malignancies. We performed a review of available literature. Immune checkpoint inhibitors represent the standard treatment for several advanced solid malignancies. However, with the exception of melanoma their clinical role in other solid malignancies is not completely clear due to the exclusion of patients with BM from approval clinical trials. Immune-checkpoint inhibitors may be an effective treatment of brain metastases of melanoma while their clinical role on brain metastases from other solid malignancies is uncertain.

scholarly journals Macrophage-Mediated Subversion of Anti-Tumour Immunity

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 747 ◽  
Author(s):  
Valeria Quaranta ◽  
Michael C. Schmid
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Tumour Progression ◽  
Immune Surveillance ◽  
Cell Types ◽  
Tumour Microenvironment ◽  
Tumour Immunity ◽  
Cell Recruitment ◽  
Clinical Benefits

Despite the incredible clinical benefits obtained by the use of immune checkpoint blockers (ICBs), resistance is still common for many types of cancer. Central for ICBs to work is activation and infiltration of cytotoxic CD8+ T cells following tumour-antigen recognition. However, it is now accepted that even in the case of immunogenic tumours, the effector functions of CD8+ T cells are highly compromised by the presence of an immunosuppressive tumour microenvironment (TME) at the tumour site. Tumour-associated macrophages (TAMs) are among the most abundant non-malignant stromal cell types within the TME and they are crucial drivers of tumour progression, metastasis and resistance to therapy. TAMs are able to regulate either directly or indirectly various aspects of tumour immunity, including T cell recruitment and functions. In this review we discuss the mechanisms by which TAMs subvert CD8+ T cell immune surveillance and how their targeting in combination with ICBs represents a very powerful therapeutic strategy.

scholarly journals Cadherin Cell Adhesion System in Canine Mammary Cancer: A Review

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Adelina Gama ◽  
Fernando Schmitt
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Mammary Cancer ◽  
Current Knowledge ◽  
Tumour Progression ◽  
Biological Functions ◽  
Canine Mammary Cancer ◽  
Organ Systems ◽  
Adhesion System

Cadherin-catenin adhesion complexes play important roles by providing cell-cell adhesion and communication in different organ systems. Abnormal expression of cadherin adhesion molecules constitutes a common phenomenon in canine mammary cancer and has been frequently implicated in tumour progression. This paper summarizes the current knowledge on cadherin/catenin adhesion molecules (E-cadherin,β-catenin, and P-cadherin) in canine mammary cancer, focusing on the putative biological functions and clinical significance of these molecules in this disease. This paper highlights the need for further research studies in this setting in order to elucidate the role of these adhesion molecules during tumour progression and metastasis.

scholarly journals Immune Cells in Cancer Therapy and Drug Delivery

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Ceren Eyileten ◽  
Kinga Majchrzak ◽  
Zofia Pilch ◽  
Katarzyna Tonecka ◽  
Joanna Mucha ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cell Proliferation ◽  
T Cells ◽  
Dendritic Cells ◽  
Immune Cells ◽  
Critical Role ◽  
Tumour Microenvironment ◽  
Cytokines And Chemokines

Recent studies indicate the critical role of tumour associated macrophages, tumour associated neutrophils, dendritic cells, T lymphocytes, and natural killer cells in tumourigenesis. These cells can have a significant impact on the tumour microenvironment via their production of cytokines and chemokines. Additionally, products secreted from all these cells have defined specific roles in regulating tumour cell proliferation, angiogenesis, and metastasis. They act in a protumour capacityin vivoas evidenced by the recent studies indicating that macrophages, T cells, and neutrophils may be manipulated to exhibit cytotoxic activity against tumours. Therefore therapy targeting these cells may be promising, or they may constitute drug or anticancer particles delivery systems to the tumours. Herein, we discussed all these possibilities that may be used in cancer treatment.

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