scholarly journals Semaphorin Signaling in Cancer-Associated Inflammation

2019 ◽  
Vol 20 (2) ◽  
pp. 377 ◽  
Author(s):  
Giulia Franzolin ◽  
Luca Tamagnone
Keyword(s):  
Immune Response ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Disease Progression ◽  
Tumor Cells ◽  
Cross Talk ◽  
Immune Cells ◽  
Major Element ◽  
Inflammatory Cells ◽  
Anti Cancer

The inflammatory and immune response elicited by the growth of cancer cells is a major element conditioning the tumor microenvironment, impinging on disease progression and patients’ prognosis. Semaphorin receptors are widely expressed in inflammatory cells, and their ligands are provided by tumor cells, featuring an intense signaling cross-talk at local and systemic levels. Moreover, diverse semaphorins control both cells of the innate and the antigen-specific immunity. Notably, semaphorin signals acting as inhibitors of anti-cancer immune response are often dysregulated in human tumors, and may represent potential therapeutic targets. In this mini-review, we provide a survey of the best known semaphorin regulators of inflammatory and immune cells, and discuss their functional impact in the tumor microenvironment.

scholarly journals Photodynamic Therapy Using a New Folate Receptor-Targeted Photosensitizer on Peritoneal Ovarian Cancer Cells Induces the Release of Extracellular Vesicles with Immunoactivating Properties

2020 ◽  
Vol 9 (4) ◽  
pp. 1185 ◽  
Author(s):  
Martha Baydoun ◽  
Olivier Moralès ◽  
Céline Frochot ◽  
Colombeau Ludovic ◽  
Bertrand Leroux ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Immune Response ◽  
Photodynamic Therapy ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Extracellular Vesicles ◽  
Immune Cells ◽  
Surgical Techniques ◽  
Ovarian Cancer Cells ◽  
The Impact

Often discovered at an advanced stage, ovarian cancer progresses to peritoneal carcinoma, which corresponds to the invasion of the serosa by multiple tumor implants. The current treatment is based on the combination of chemotherapy and tumor cytoreduction surgery. Despite the progress and standardization of surgical techniques combined with effective chemotherapy, post-treatment recurrences affect more than 60% of women in remission. Photodynamic therapy (PDT) has been particularly indicated for the treatment of superficial lesions on large surfaces and appears to be a relevant candidate for the treatment of microscopic intraperitoneal lesions and non-visible lesions. However, the impact of this therapy on immune cells remains unclear. Hence, the objective of this study is to validate the efficacy of a new photosensitizer [pyropheophorbide a-polyethylene glycol-folic acid (PS)] on human ovarian cancer cells and to assess the impact of the secretome of PDT-treated cells on human peripheral blood mononuclear cells (PBMC). We show that PS, upon illumination, can induce cell death of different ovarian tumor cells. Furthermore, PDT using this new PS seems to favor activation of the immune response by inducing the secretion of effective cytokines and inhibiting the pro-inflammatory and immunosuppressive ones, as well as releasing extracellular vesicles (EVs) prone to activating immune cells. Finally, we show that PDT can activate CD4+ and CD8+ T cells, resulting in a potential immunostimulating process. The results of this pilot study therefore indicate that PS-PDT treatment may not only be effective in rapidly and directly destroying target tumor cells but also promote the activation of an effective immune response; notably, by EVs. These data thus open up good prospects for the treatment of micrometastases of intraperitoneal ovarian carcinosis which are currently inoperable.

scholarly journals Shaping Immune Responses in the Tumor Microenvironment of Ovarian Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Xin Luo ◽  
Jing Xu ◽  
Jianhua Yu ◽  
Ping Yi
Keyword(s):  
Ovarian Cancer ◽  
Tumor Microenvironment ◽  
Immune Responses ◽  
Cancer Cells ◽  
Disease Progression ◽  
Immune Cells ◽  
Biomarker Discovery ◽  
Immune Cell ◽  
Ovarian Cancer Cells ◽  
Cancer Tumor

Reciprocal signaling between immune cells and ovarian cancer cells in the tumor microenvironment can alter immune responses and regulate disease progression. These signaling events are regulated by multiple factors, including genetic and epigenetic alterations in both the ovarian cancer cells and immune cells, as well as cytokine pathways. Multiple immune cell types are recruited to the ovarian cancer tumor microenvironment, and new insights about the complexity of their interactions have emerged in recent years. The growing understanding of immune cell function in the ovarian cancer tumor microenvironment has important implications for biomarker discovery and therapeutic development. This review aims to describe the factors that shape the phenotypes of immune cells in the tumor microenvironment of ovarian cancer and how these changes impact disease progression and therapy.

Extracellular vesicles in cancer progression: are they part of the problem or part of the solution?

Nanomedicine ◽  
2020 ◽  
Vol 15 (26) ◽  
pp. 2625-2641
Author(s):  
Juliete Nathali Scholl ◽  
Camila Kehl Dias ◽  
Laurent Muller ◽  
Ana Maria Oliveira Battastini ◽  
Fabrício Figueiró
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Immune Cells ◽  
Cell Function ◽  
Cytokine Release

Extracellular vesicles (EVs) are released especially by cancer cells. They modulate the tumor microenvironment by interacting with immune cells while carrying immunosuppressive or immunostimulatory molecules. In this review, we will explore some conflicting reports regarding the immunological outcomes of EVs in cancer progression, in which they might initiate an antitumor immune response or an immunosuppressive response. Concerning immunosuppression, the role of tumor-derived EVs’ in the adenosinergic system is underexplored. The enhancement of adenosine (ADO) levels in the tumor microenvironment impairs T-cell function and cytokine release. However, some tumor-derived EVs may deliver immunostimulatory factors, promoting immunogenic activity, even with ADO production. The modulatory role of ADO over the tumor progression represents a piece in an intricate microenvironment with anti and pro tumoral seesaw-like mechanisms.

scholarly journals Cross-Talk Between Tumor Cells Undergoing Epithelial to Mesenchymal Transition and Natural Killer Cells in Tumor Microenvironment in Colorectal Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Ana Vuletić ◽  
Katarina Mirjačić Martinović ◽  
Nevena Tišma Miletić ◽  
Jerome Zoidakis ◽  
Sergi Castellvi-Bel ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Microenvironment ◽  
Nk Cells ◽  
Natural Killer ◽  
Tumor Cells ◽  
Cross Talk ◽  
Immune Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Nk Cell ◽  
Mesenchymal Transition

Tumor cells undergoing epithelial to mesenchymal transition (EMT) and immune cells in tumor microenvironment (TME) reciprocally influence each other. Immune cells, by supplying TME with bioactive molecules including cytokines, chemokines, enzymes, metabolites, and by physical interactions with tumor cells via their receptors, represent an important factor that affects EMT. Chronical inflammation in TME favorizes tumor growth and invasiveness and stimulates synthesis of EMT promoting transcription factors. Natural killer (NK) cells, owing to their unique ability to exert cytotoxic function independent of major histocompatibility (MHC)-mediated antigen presentation, play a significant role in the control of metastasis in colorectal cancer (CRC). Although, the cross-talk between immune cells and tumor cells in general favors the induction of EMT and inhibition of antitumor immune responses, there are some changes in the immunogenicity of tumor cells during EMT of CRC cells that increase their susceptibility to NK cell cytotoxic lysis. However, suppressive TME downmodulates the expression of activating NK cell receptors, decreases the expression of activating and increases the expression of inhibitory NK cell ligands on tumor cells, and impairs NK cell metabolism that altogether negatively affects the overall NK cell function. Furthermore, process of EMT is often associated with increased expression of programmed cell death ligand (PD-L) and expression of immune checkpoint molecules PD-1, TIGIT, and TIM3 on functionally exhausted NK cells in TME in CRC. In this review we discuss modalities of cross-talk between tumor cells and NK cells, with regard of EMT-driven changes.

scholarly journals Associated with Immune Function, miR-150-5p is a Favorable Biomarker for Head and Neck Cancer Patients

2021 ◽  
Author(s):  
Zhi-Jie Liu ◽  
Li-Sheng Li-Sheng ◽  
Jing Wang ◽  
Li-Xia Peng ◽  
Yan Mei ◽  
...  
Keyword(s):  
Immune Response ◽  
Squamous Cell Carcinoma ◽  
B Cells ◽  
Tumor Microenvironment ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Tumor Cells ◽  
Squamous Cell ◽  
Cross Talk ◽  
Neck Squamous Cell Carcinoma

Abstract BackgroundAccumulating evidence has shown that dysregulated expression of microRNAs plays a key role in tumorigenesis. To explore the mechanisms of this we conducted this study.MethodsFive Gene Expression Omnibus datasets (GEO) datasets , GSE32960, GSE36682, GSE43039, GSE70970 and GSE118613 and head and neck squamous cell carcinoma data of The Cancer Genome Atlas (TCGA) were analysis in this study.ResultsBy analyzing the microRNA expression profile of nasopharyngeal carcinoma (NPC) in the five GEO datasets, we identified miR-150-5p as potential biomarker for patient survival. To explore the mechanisms of this, We examined the head and neck squamous cell carcinoma data of TCGA and found that miR-150-5p was correlated with high enrichment of tumor-infiltrating B cells, low enrichment of cancer-associated fibroblasts and down-regulated oncogenic pathways. miR-150-5p may also improve the immune response in the tumor microenvironment. These findings may explain how miR-150-5p improves outcome of head and neck squamous cell carcinoma patients including NPC. Additionally, the exosomal long non-coding RNA AC073130.1 was identified as a potential regulator of miR-150-5p. As miR-150-5p can also be released via exosomes, this study provides insight into the cross-talk of tumor cells and B cells in the tumor microenvironment via exosomal AC073130.1 and miR-150-5p. ConclusionMiR-150-5p improves outcome of head and neck squamous cell carcinoma patients by improving the immune response. There might be a cross-talk of tumor cells and B cells in the tumor microenvironment via exosomal AC073130.1 and miR-150-5p.

scholarly journals Metabolism of Immune Cells in the Tumor Microenvironment

2021 ◽  
pp. 173-185
Author(s):  
Jin G. Jung ◽  
Anne Le
Keyword(s):  
Extracellular Matrix ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Immune Cells ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Tumor Biology ◽  
Determinant Factor

AbstractThe tumor microenvironment (TME) is a complex biological structure surrounding tumor cells and includes blood vessels, immune cells, fibroblasts, adipocytes, and extracellular matrix (ECM) [1, 2]. These heterogeneous surrounding structures provide nutrients, metabolites, and signaling molecules to provide a cancer-friendly environment. The metabolic interplay between immune cells and cancer cells in the TME is a key feature not only for understanding tumor biology but also for discovering cancer cells’ vulnerability. As cancer immunotherapy to treat cancer patients and the use of metabolomics technologies become more and more common [3], the importance of the interplay between cancer cells and immune cells in the TME is emerging with respect to not only cell-to-cell interactions but also metabolic pathways. This interaction between immune cells and cancer cells is a complex and dynamic process in which immune cells act as a determinant factor of cancer cells’ fate and vice versa. In this chapter, we provide an overview of the metabolic interplay between immune cells and cancer cells and discuss the therapeutic opportunities as a result of this interplay in order to define targets for cancer treatment. It is important to understand and identify therapeutic targets that interrupt this cancerpromoting relationship between cancer cells and the surrounding immune cells, allowing for maximum efficacy of immune checkpoint inhibitors as well as other genetic and cellular therapies.

scholarly journals Exosome-Mediated Crosstalk Between Tumor and Tumor-Associated Macrophages

2021 ◽  
Vol 8 ◽  
Author(s):  
Qi Chen ◽  
Yuefeng Li ◽  
Wujiang Gao ◽  
Lu Chen ◽  
Wenlin Xu ◽  
...  
Keyword(s):  
Amino Acids ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Immune Cells ◽  
Tumor Treatment ◽  
Cellular Functions ◽  
Tumor Associated Macrophages ◽  
Cancer Types ◽  
Cell Dissemination

Exosomes are nanosized vesicles, derived from the endolysosomal compartment of cells and can shuttle diverse biomolecules such as nucleic acids, proteins, lipids, amino acids, and metabolites, which can reflect their origin cells. Delivery of these cargoes to recipient cells enables exosomes to influence diverse cellular functions. As one of the most abundant immune cells in the tumor microenvironment, tumor-associated macrophages (TAMs) are educated by the tumor milieu, which is rich in cancer cells and stroma components, to exert functions such as the promotion of tumor growth, immunosuppression, angiogenesis, and cancer cell dissemination. Herein, we focus on exosomes-mediated intercellular communication between tumor cells and TAM in the tumor microenvironment, which may provide new targets for anti-tumor treatment. In this review, we highlight the most recent studies on the effect of tumor/macrophage-derived exosomes on macrophage/tumor function in different cancer types.

scholarly journals Immune and Inflammatory Cells in Thyroid Cancer Microenvironment

2019 ◽  
Vol 20 (18) ◽  
pp. 4413 ◽  
Author(s):  
Ferrari ◽  
Fallahi ◽  
Galdiero ◽  
Ruffilli ◽  
Elia ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Immune System ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Immune Cells ◽  
Checkpoint Inhibitors ◽  
Diagnostic Procedures ◽  
Inflammatory Cells ◽  
Cytotoxic Lymphocytes ◽  
Cytokines And Chemokines

A hallmark of cancer is the ability of tumor cells to avoid immune destruction. Activated immune cells in tumor microenvironment (TME) secrete proinflammatory cytokines and chemokines which foster the proliferation of tumor cells. Specific antigens expressed by cancer cells are recognized by the main actors of immune response that are involved in their elimination (immunosurveillance). By the recruitment of immunosuppressive cells, decreasing the tumor immunogenicity, or through other immunosuppressive mechanisms, tumors can impair the host immune cells within the TME and escape their surveillance. Within the TME, cells of the innate (e.g., macrophages, mast cells, neutrophils) and the adaptive (e.g., lymphocytes) immune responses are interconnected with epithelial cancer cells, fibroblasts, and endothelial cells via cytokines, chemokines, and adipocytokines. The molecular pattern of cytokines and chemokines has a key role and could explain the involvement of the immune system in tumor initiation and progression. Thyroid cancer-related inflammation is an important target for diagnostic procedures and novel therapeutic strategies. Anticancer immunotherapy, especially immune checkpoint inhibitors, unleashes the immune system and activates cytotoxic lymphocytes to kill cancer cells. A better knowledge of the molecular and immunological characteristics of TME will allow novel and more effective immunotherapeutic strategies in advanced thyroid cancer.

scholarly journals Downregulation of Immune Response- and External Stimulus-Related Genes in CRC Organoids, and Their Re-Expression by Co-Culturing with CAFs

2020 ◽  
Author(s):  
Mie Naruse ◽  
Masako Ochiai ◽  
Shigeki Sekine ◽  
Hirokazu Taniguchi ◽  
Teruhiko Yoshida ◽  
...  
Keyword(s):  
Immune Response ◽  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Culture System ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
External Stimulus ◽  
Preclinical Model ◽  
Tumor Tissues ◽  
Anti Cancer

Abstract Organoids derived from epithelial tumors have recently been utilized as a preclinical model in basic and translational studies. This model is considered to reproduce the features of cell-cell contacted and differentiated original tumor cells, but not the tumor microenvironment. In this study, we established organoids and paired cancer-associated fibroblasts (CAFs) from surgical specimens of colorectal carcinomas (CRCs), and evaluated gene expression profiles in organoids with and without co-culture with CAFs to assess interactions between tumor cells and CAFs in tumor tissues. We found that the expression levels of several genes, which are highly expressed in original CRC tissues, were downregulated in organoids but re-expressed by co-culturing with CAFs. They comprised immune response- and external stimulus-related genes, e.g., REG family and dual oxidases (DUOXs), which are known to have malignant functions, e.g., cell-proliferation and/or reducing apoptosis of epithelia and drug resistance for anti-cancer drugs in tumors. In addition, the degree of re-production of REG1 and DUOX2 in the co-culture system varied depending on CAFs from each CRC case. In conclusion, the co-culture system of CRC organoids with paired CAFs was able to partially reproduce the tumor microenvironment.

Immune profile of tumor and chemotherapy

2018 ◽  
Vol 3 (2) ◽  
pp. 54
Author(s):  
Bakulesh Khamar
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Immune Cells ◽  
Prognostic Value ◽  
Cell Mediated Immunity ◽  
Cell Mediated Immune Response ◽  
Current Classification ◽  
Immunosuppressive Cells

<p>Chemotherapy works through its activity on cancer cells. It generally suppresses cell-mediated immunity but also improves cell-mediated immune response by making tumor cells vulnerable to killing by cell-mediated immune responses as well as through its action on immunostimulant and immunosuppressive cells. Outcome of chemotherapy seems to be dependent on baseline tumor-infiltrating immune cells (TII) as well as changes in TII following chemotherapy in varieties of tumors. Evaluation of density and site of two TII is done in immunoscore. It is a better marker than evaluation of a single TII. Evaluation of TII can have prognostic and predictive value and can help in the better stratifying prognostic value of current classification.</p>

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