The expressions of IDO1/TDO2 in tumour cells and tumour microenvironment are associated with MCPyV status and prognosis in Merkel cell carcinomas

2018 ◽  
Author(s):  
Lusi Oka Wardhani
Keyword(s):  
Tumour Microenvironment ◽  
Tumour Cells ◽  
Merkel Cell

scholarly journals Therapeutic Targeting of the Tumour Microenvironment in Metastatic Colorectal Cancer

2021 ◽  
Vol 22 (4) ◽  
pp. 2067
Author(s):  
Rhynelle S. Dmello ◽  
Sarah Q. To ◽  
Ashwini L. Chand
Keyword(s):  
Colorectal Cancer ◽  
Targeted Therapy ◽  
Liver Metastasis ◽  
Metastatic Colorectal Cancer ◽  
Tumour Microenvironment ◽  
Tumour Cells ◽  
Cellular Interactions ◽  
Circulating Tumour Cells ◽  
Therapeutic Targeting ◽  
Colorectal Cancer Patients

Liver metastasis is the primary contributor to the death of patients with colorectal cancer. Despite the overall success of current treatments including targeted therapy, chemotherapy, and immunotherapy combinations in colorectal cancer patients, the prognosis of patients with liver metastasis remains poor. Recent studies have highlighted the importance of the tumour microenvironment and the crosstalk within that determines the fate of circulating tumour cells in distant organs. Understanding the interactions between liver resident cells and tumour cells colonising the liver opens new therapeutic windows for the successful treatment of metastatic colorectal cancer. Here we discuss critical cellular interactions within the tumour microenvironment in primary tumours and in liver metastases that highlight potential therapeutic targets. We also discuss recent therapeutic advances for the treatment of metastatic colorectal cancer.

scholarly journals Activation of blood coagulation in cancer: implications for tumour progression

2013 ◽  
Vol 33 (5) ◽  
Author(s):  
Luize G. Lima ◽  
Robson Q. Monteiro
Keyword(s):  
Blood Coagulation ◽  
Tumour Progression ◽  
Primary Tumour ◽  
Tumour Microenvironment ◽  
Tumour Cells ◽  
Protease Activated Receptors ◽  
Tumour Metastasis ◽  
Coagulation Proteins ◽  
Associated Proteins ◽  
Cancer Associated Thrombosis

Several studies have suggested a role for blood coagulation proteins in tumour progression. Herein, we discuss (1) the activation of the blood clotting cascade in the tumour microenvironment and its impact on primary tumour growth; (2) the intravascular activation of blood coagulation and its impact on tumour metastasis and cancer-associated thrombosis; and (3) antitumour therapies that target blood-coagulation-associated proteins. Expression levels of the clotting initiator protein TF (tissue factor) have been correlated with tumour cell aggressiveness. Simultaneous TF expression and PS (phosphatidylserine) exposure by tumour cells promote the extravascular activation of blood coagulation. The generation of blood coagulation enzymes in the tumour microenvironment may trigger the activation of PARs (protease-activated receptors). In particular, PAR1 and PAR2 have been associated with many aspects of tumour biology. The procoagulant activity of circulating tumour cells favours metastasis, whereas the release of TF-bearing MVs (microvesicles) into the circulation has been correlated with cancer-associated thrombosis. Given the role of coagulation proteins in tumour progression, it has been proposed that they could be targets for the development of new antitumour therapies.

scholarly journals Exosome in Tumour Microenvironment: Overview of the Crosstalk between Normal and Cancer Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Catarina Roma-Rodrigues ◽  
Alexandra R. Fernandes ◽  
Pedro Viana Baptista
Keyword(s):  
Invasive Procedure ◽  
Tumour Microenvironment ◽  
Minimal Invasive ◽  
Tumour Cells ◽  
Bioactive Molecules ◽  
Anatomical Location ◽  
Cell Of Origin ◽  
Diagnosis And Prognosis ◽  
Multistep Process ◽  
Mesenchymal Transformation

Cancer development is a multistep process in which exosomes play important roles. Exosomes are small vesicles formed in vesicular bodies in the endosomal network. The major role of exosomes seems to be the transport of bioactive molecules between cells. Depending on the cell of origin, exosomes are implicated in the regulation of several cellular events, with phenotypic consequences in recipient cells. Cancer derived exosomes (CCEs) are important players in the formation of the tumour microenvironment by (i) enabling the escape of tumour cells to immunological system and help initiating the inflammatory response; (ii) acting in the differentiation of fibroblasts and mesenchymal cells into myofibroblasts; (iii) triggering the angiogenic process; and (iv) enhancing the metastatic evolution of the tumour by promoting epithelial to mesenchymal transformation of tumour cells and by preparing the tumour niche in the new anatomical location. Since the finding that exosomes content resembles that of the cell of origin, they may be regarded as suitable biomarkers for cancer diagnosis, allowing for diagnosis and prognosis via a minimal invasive procedure. Exosome involvement in cancer may open new avenues regarding therapeutics, such as vectors for targeted drug delivery.

scholarly journals ApoE-TREM2 axis induces pathogenic senescent-like myeloid cells in prostate cancer

2021 ◽  
Author(s):  
Arianna Calcinotto ◽  
Nicolò Bancaro ◽  
Martina Troiani ◽  
Rydell Arzola ◽  
Angela Rita Elia ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Histone Deacetylase Inhibitors ◽  
Tumour Progression ◽  
Myeloid Cells ◽  
Suppressor Cells ◽  
Treatment Resistance ◽  
Tumour Microenvironment ◽  
Tumour Cells ◽  
Mrna Levels ◽  
Immature Myeloid Cells

Abstract Tumour cells promote the expansion and intra-tumoural recruitment of Myeloid-derived suppressor cells (MDSCs), a subset of immature myeloid cells, that support tumour cell proliferation and confer treatment resistance. While immature myeloid cells have a very short lifespan, whether pathogenic MDSCs can persist in the tumour microenvironment remains unknown. Here, we report the identification of a subset of long-lasting MDSCs that upregulate markers of cellular senescence and the TREM2 receptor. Senescent-like MDSCs possess higher pro-inflammatory capabilities compared to canonical MDSCs. Genetic and pharmacological elimination of senescent-like MDSCs decreases tumour progression in different mouse models of prostate cancer. Mechanistically, we find that Apolipoprotein E (ApoE) secreted by prostate tumour cells binds TREM2 in senescent-like MDSCs, thereby regulating the survival of these cells. ApoE and TREM2 mRNA levels are upregulated in prostate cancers and correlate with poor patients’ prognosis. Taken together, these results reveal a novel mechanism by which the tumour microenvironment shapes the intra-tumoural immune response. Pathogenic senescent-like MDSCs persist longer in the tumour microenvironment and can be eliminated by histone deacetylase inhibitors enhancing the efficacy of standard therapy in prostate cancer.

scholarly journals Immune Classification for the PD-L1 Expression and Tumour-Infiltrating Lymphocytes in Colorectal Adenocarcinoma

2019 ◽  
Author(s):  
Byeong-Joo Noh ◽  
Jae Young Kwak ◽  
Dae-Woon Eom
Keyword(s):  
Colorectal Adenocarcinoma ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Tumour Microenvironment ◽  
Tumour Cells ◽  
Effective Response ◽  
Recent Emergence ◽  
Tumour Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes ◽  
Colorectal Adenocarcinomas

Abstract Background Colorectal adenocarcinoma is the third most common cancer worldwide and a leading cause of cancer-related death. The recent emergence of diverse immunotherapeutic agents has made it crucial to interpret a complex tumour microenvironment intermingled with tumour-infiltrating immune cells to predict the immunotherapeutic response rate. However, in colorectal adenocarcinoma, studies are lacking that provide detailed analyses of programmed death-ligand 1 (PD-L1) and tumour-infiltrating lymphocytes (TIL) to elucidate their prognostic values and to identify immunotherapy-targetable subgroups, preferably with multiple immune-related biomarkers. In the present study, we categorize colorectal adenocarcinomas into four types of tumour immune microenvironments according to PD-L1 expression and TIL, analyse their prognostic values, and propose an immunotherapy-targetable subgroup.Methods Formalin-fixed, paraffin-embedded tissue samples of surgically resected primary colorectal adenocarcinomas (n = 489) were obtained and arrayed on tissue microarray blocks. Immunohistochemical stains for PD-L1, programmed cell death protein 1 (PD-1), cluster of differentiation 8 (CD8), and microsatellite instability (MSI) were performed and evaluated.Results Tumour microenvironment immune type (TMIT) I (PD-L1-positive tumour cells and CD8-high TIL) and type II (PD-L1-negative tumour cells and CD8-low TIL) showed the best and worst prognoses, respectively. PD-L1 overexpression was significantly associated with MSI status. PD-L1 immunoreactivity was positively correlated with TIL having CD8 or PD-1 overexpression.Conclusions TMIT I subgroup showed stronger CD8/PD-L1/PD-1 signalling interaction compared to the other TMIT. Therefore, we propose that the TMIT I subgroup is a candidate TMIT to predict effective response rate for existing immune checkpoint inhibitors and determine targetable subgroups for emerging therapies.

Adenosine Receptors as Novel Targets for the Treatment of Various Cancers

2019 ◽  
Vol 25 (26) ◽  
pp. 2828-2841 ◽  
Author(s):  
Bapi Gorain ◽  
Hira Choudhury ◽  
Gan Sook Yee ◽  
Subrat Kumar Bhattamisra
Keyword(s):  
Cancer Progression ◽  
Adenosine Receptors ◽  
Antitumour Activity ◽  
Cell Activity ◽  
Tumour Microenvironment ◽  
Tumour Cells ◽  
The Body ◽  
Active Components ◽  
High Concentration ◽  
Tumour Proliferation

Adenosine is a ubiquitous signaling nucleoside molecule, released from different cells within the body to act on vasculature and immunoescape. The physiological action on the proliferation of tumour cell has been reported by the presence of high concentration of adenosine within the tumour microenvironment, which results in the progression of the tumour, even leading to metastases. The activity of adenosine exclusively depends upon the interaction with four subtypes of heterodimeric G-protein-coupled adenosine receptors (AR), A1, A2A, A2B, and A3-ARs on the cell surface. Research evidence supports that the activation of those receptors via specific agonist or antagonist can modulate the proliferation of tumour cells. The first category of AR, A1 is known to play an antitumour activity via tumour-associated microglial cells to prevent the development of glioblastomas. A2AAR are found in melanoma, lung, and breast cancer cells, where tumour proliferation is stimulated due to inhibition of the immune response via inhibition of natural killer cells cytotoxicity, T cell activity, and tumourspecific CD4+/CD8+ activity. Alternatively, A2BAR helps in the development of tumour upon activation via upregulation of angiogenin factor in the microvascular endothelial cells, inhibition of MAPK and ERK 1/2 phosphorylation activity. Lastly, A3AR is expressed in low levels in normal cells whereas the expression is upregulated in tumour cells, however, agonists to this receptor inhibit tumour proliferation through modulation of Wnt and NF-κB signaling pathways. Several researchers are in search for potential agents to modulate the overexpressed ARs to control cancer. Active components of A2AAR antagonists and A3AR agonists have already entered in Phase-I clinical research to prove their safety in human. This review focused on novel research targets towards the prevention of cancer progression through stimulation of the overexpressed ARs with the hope to protect lives and advance human health.

Radiotherapy-induced immunogenic effects in bladder cancer.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 418-418
Author(s):  
Richard Walshaw ◽  
Jamie Honeychurch ◽  
Joanne Roberts ◽  
Jacqueline Swan ◽  
Laura Dean ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
De Novo ◽  
Antigen Expression ◽  
Tumour Microenvironment ◽  
Tumour Cells ◽  
Surface Proteins ◽  
Orthotopic Model ◽  
Mhc I ◽  
Clinical Model

418 Background: Many patients with bladder cancer (BC) undergo radiotherapy (RT) during the course of their treatment. There is emerging evidence that RT can cause immune stimulatory changes within the tumour microenvironment (TME), potentially contributing to its efficacy. We aimed to determine if RT induces immunogenic changes in murine BC cell lines, and develop a pre-clinical model of BC with a TME reflective of de novo tumours in order to test this premise in vivo. Methods: Immunogenic effects of RT were determined using murine vaccination studies with irradiated tumour cells. RT-induced immuno-phenotypic changes in surface antigen expression on tumour cells were ascertained using flow cytometry. An orthotopic BC model was established using MBT2 cells instilled intravesically in C3H/Hen mice, and resulting tumours monitored with ultrasound (US). We used immunohistochemical (IHC) staining to determine the immune contexture of the TME within developing orthotopic tumours. Results: C57BL/6 mice inoculated with irradiated MB49 cells demonstrated improved survival compared to control mice after subsequent rechallenge with viable tumour cells. This effect was not seen in C3H mice implanted with irradiated MBT2 cells. RT led to upregulation of immune stimulatory molecules CD80, MHC I, and Fas on MB49 but not MBT2 cells. Tumours developed in 80% of mice following catheter implant, and visible on US 3-4 weeks after instillation. Profiling of the TME with IHC demonstrated that tumours contained few CD8+ T-cells, but high numbers of myeloid cells. Conclusions: RT induces immune stimulatory effects on murine BC cells, including upregulation of several surface proteins. In future work, we will determine the effects of RT on the TME in the orthotopic model, and correlate these with the expression of various immunogenic cell surface proteins. This may lead to the discovery of a biomarker to predict which patients with BC would benefit from combination of an immunomodulatory agent with RT.

scholarly journals Mechanisms of tumour escape from immune surveillance

2016 ◽  
Vol 60 (4) ◽  
pp. 453-460 ◽  
Author(s):  
Urszula Lisiecka ◽  
Krzysztof Kostro
Keyword(s):  
Immune Surveillance ◽  
Treatment Method ◽  
Tumour Microenvironment ◽  
Tumour Cells ◽  
The Body ◽  
Host Cells ◽  
Entire Body ◽  
Adaptive Responses ◽  
Tumour Escape ◽  
Progressive Growth

Abstract The progressive growth and spread of tumour cells in the form of metastases requires an interaction of healthy host cells, such as endothelial cells, fibroblasts, and other cells of mesenchymal origin with immune cells taking part in innate and adaptive responses within the tumour lesion and entire body. The host cells interact with tumour cells to create a dynamic tumour microenvironment, in which healthy cells can both positively and negatively influence the growth and spread of the tumour. The balance of cellular homeostasis and the effect of substances they secrete on the tumour microenvironment determine whether the tumour has a tendency to grow or disappear, and whether the cells remain within the lesion or are capable of metastasis to other regions of the body. Intercellular interactions also determine the tumour’s susceptibility to radiation or other types of cancer treatment. They may also be a rational explanation for differences in treatment outcomes, in which some metastases regress and others progress in response to the same treatment method.

scholarly journals Does the Microenvironment Hold the Hidden Key for Functional Precision Medicine in Pancreatic Cancer?

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2427
Author(s):  
John Kokkinos ◽  
Anya Jensen ◽  
George Sharbeen ◽  
Joshua A. McCarroll ◽  
David Goldstein ◽  
...  
Keyword(s):  
Precision Medicine ◽  
Ex Vivo ◽  
Performance Status ◽  
Treatment Options ◽  
Critical Role ◽  
Tumour Microenvironment ◽  
Tumour Cells ◽  
Ductal Adenocarcinoma ◽  
Preclinical Models ◽  
Culture Models

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers and no significant improvement in patient survival has been seen in the past three decades. Treatment options are limited and selection of chemotherapy in the clinic is usually based on the performance status of a patient rather than the biology of their disease. In recent years, research has attempted to unlock a personalised treatment strategy by identifying actionable molecular targets in tumour cells or using preclinical models to predict the effectiveness of chemotherapy. However, these approaches rely on the biology of PDAC tumour cells only and ignore the importance of the microenvironment and fibrotic stroma. In this review, we highlight the importance of the microenvironment in driving the chemoresistant nature of PDAC and the need for preclinical models to mimic the complex multi-cellular microenvironment of PDAC in the precision medicine pipeline. We discuss the potential for ex vivo whole-tissue culture models to inform precision medicine and their role in developing novel therapeutic strategies that hit both tumour and stromal compartments in PDAC. Thus, we highlight the critical role of the tumour microenvironment that needs to be addressed before a precision medicine program for PDAC can be implemented.

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