scholarly journals Tumor-intrinsic signaling pathways: key roles in the regulation of the immunosuppressive tumor microenvironment

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Li Yang ◽  
Aitian Li ◽  
Qingyang Lei ◽  
Yi Zhang
Keyword(s):  
Tumor Microenvironment ◽  
Molecular Mechanisms ◽  
Immune Escape ◽  
Tumor Immune Escape ◽  
Specific Tumor ◽  
Recent Developments ◽  
Immunosuppressive Tumor Microenvironment ◽  
Immune Exclusion ◽  
And Function ◽  
Immunosuppressive Cells

AbstractImmunotherapy is a currently popular treatment strategy for cancer patients. Although recent developments in cancer immunotherapy have had significant clinical impact, only a subset of patients exhibits clinical response. Therefore, understanding the molecular mechanisms of immunotherapy resistance is necessary. The mechanisms of immune escape appear to consist of two distinct tumor characteristics: a decrease in effective immunocyte infiltration and function and the accumulation of immunosuppressive cells in the tumor microenvironment. Several host-derived factors may also contribute to immune escape. Moreover, inter-patient heterogeneity predominantly results from differences in somatic mutations between cancers, which has led to the hypothesis that differential activation of specific tumor-intrinsic pathways may explain the phenomenon of immune exclusion in a subset of cancers. Increasing evidence has also shown that tumor-intrinsic signaling plays a key role in regulating the immunosuppressive tumor microenvironment and tumor immune escape. Therefore, understanding the mechanisms underlying immune avoidance mediated by tumor-intrinsic signaling may help identify new therapeutic targets for expanding the efficacy of cancer immunotherapies.

scholarly journals Immunosuppressive Roles of Galectin-1 in the Tumor Microenvironment

Biomolecules ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1398
Author(s):  
Yanyu Huang ◽  
Hsiao-Chi Wang ◽  
Junwei Zhao ◽  
Ming-Heng Wu ◽  
Tsung-Chieh Shih
Keyword(s):  
Tumor Microenvironment ◽  
Cell Function ◽  
Immune Cell ◽  
Immune Escape ◽  
Immune Surveillance ◽  
Human Tumor ◽  
Immune Cell Function ◽  
Tumor Immune Escape ◽  
Cancer Tumor ◽  
And Function

Evasion of immune surveillance is an accepted hallmark of tumor progression. The production of immune suppressive mediators by tumor cells is one of the major mechanisms of tumor immune escape. Galectin-1 (Gal-1), a pivotal immunosuppressive molecule, is expressed by many types of cancer. Tumor-secreted Gal-1 can bind to glycosylated receptors on immune cells and trigger the suppression of immune cell function in the tumor microenvironment, contributing to the immune evasion of tumors. The aim of this review is to summarize the current literature on the expression and function of Gal-1 in the human tumor microenvironment, as well as therapeutics targeting Gal-1.

scholarly journals Cancer-Associated Fibroblasts Promote the Upregulation of PD-L1 Expression Through Akt Phosphorylation in Colorectal Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Yang Gao ◽  
Zhao Sun ◽  
Junjie Gu ◽  
Zhe Li ◽  
Xiuxiu Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Microenvironment ◽  
Molecular Mechanisms ◽  
Immune Escape ◽  
Disease Free Survival ◽  
Epithelial Tissue ◽  
Cancer Associated Fibroblasts ◽  
Tumor Immune Escape ◽  
Akt Phosphorylation

Upregulation of immune checkpoint proteins is one of the main mechanisms for tumor immune escape. The expression of programmed death ligand-1 (PD-L1) in colorectal cancer (CRC) is higher than in normal colorectal epithelial tissue, and patients with higher PD-L1 expression have a poorer prognosis. Additionally, PD-L1 expression in CRC is affected by the tumor microenvironment (TME). As a major component of the TME, cancer-associated fibroblasts (CAFs) can act as immune regulators and generate an immunosuppressive tumor microenvironment. Therefore, we speculated that CAFs may be related to the upregulation of PD-L1 in CRC, which leads to tumor immune escape. We found that CAFs upregulate PD-L1 expression in CRC cells through AKT phosphorylation, thereby reducing the killing of CRC cells by peripheral blood mononuclear cells. The ratio of CAFs to CRC cells was positively correlated with AKT phosphorylation and the expression of PD-L1 in CRC in vitro. Consistent with the in vitro results, high CAF content and high expression of PD-L1 were negatively correlated with disease-free survival (DFS) of CRC patients. These results indicate that the upregulation of PD-L1 expression in CRC by CAFs through the activation of Akt is one of the molecular mechanisms of tumor immune escape. Thus, targeted anti-CAF therapy may help improve the efficacy of immunotherapy.

scholarly journals Next frontier in tumor immunotherapy: macrophage-mediated immune evasion

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Yingqi Qiu ◽  
Tong Chen ◽  
Rong Hu ◽  
Ruiyi Zhu ◽  
Chujun Li ◽  
...  
Keyword(s):  
Immune Evasion ◽  
Immune Escape ◽  
Tumor Immunotherapy ◽  
Immune Checkpoints ◽  
Cancer Treatments ◽  
Tumor Immune Escape ◽  
Tumor Immune Evasion ◽  
New Ideas ◽  
And Function ◽  
Immunosuppressive Cells

AbstractTumor-associated macrophages (TAMs), at the core of immunosuppressive cells and cytokines networks, play a crucial role in tumor immune evasion. Increasing evidences suggest that potential mechanisms of macrophage-mediated tumor immune escape imply interpretation and breakthrough to bottleneck of current tumor immunotherapy. Therefore, it is pivotal to understand the interactions between macrophages and other immune cells and factors for enhancing existing anti-cancer treatments. In this review, we focus on the specific signaling pathways through which TAMs involve in tumor antigen recognition disorders, recruitment and function of immunosuppressive cells, secretion of immunosuppressive cytokines, crosstalk with immune checkpoints and formation of immune privileged sites. Furthermore, we summarize correlative pre-clinical and clinical studies to provide new ideas for immunotherapy. From our perspective, macrophage-targeted therapy is expected to be the next frontier of cancer immunotherapy.

scholarly journals Role of the tumor microenvironment in PD-L1/PD-1-mediated tumor immune escape

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Xianjie Jiang ◽  
Jie Wang ◽  
Xiangying Deng ◽  
Fang Xiong ◽  
Junshang Ge ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Immune Escape ◽  
Tumor Immune Escape

New functions for old factors: the role of polyamines during the establishment of pregnancy

2019 ◽  
Vol 31 (7) ◽  
pp. 1228
Author(s):  
Jane C. Fenelon ◽  
Bruce D. Murphy
Keyword(s):  
Molecular Mechanisms ◽  
New Technologies ◽  
Alternative Pathway ◽  
Rapid Expansion ◽  
Polyamine Synthesis ◽  
Recent Developments ◽  
And Function ◽  
Implantation Period ◽  
Synthesis Regulation

Implantation is essential for the establishment of a successful pregnancy, and the preimplantation period plays a significant role in ensuring implantation occurs in a timely and coordinated manner. This requires effective maternal–embryonic signalling, established during the preimplantation period, to synchronise development. Although multiple factors have been identified as present during this time, the exact molecular mechanisms involved are unknown. Polyamines are small cationic molecules that are ubiquitously expressed from prokaryotes to eukaryotes. Despite being first identified over 300 years ago, their essential roles in cell proliferation and growth, including cancer, have only been recently recognised, with new technologies and interest resulting in rapid expansion of the polyamine field. This review provides a summary of our current understanding of polyamine synthesis, regulation and function with a focus on recent developments demonstrating the requirements for polyamines during the establishment of pregnancy up to the implantation stage, in particular the role of polyamines in the control of embryonic diapause and the identification of an alternative pathway for their synthesis in sheep pregnancy. This, along with other novel discoveries, provides new insights into the control of the peri-implantation period in mammals and highlights the complexities that exist in regulating this critical period of pregnancy.

scholarly journals Molecular Mechanism and Potential Targets for Blocking HPV-Induced Lesion Development

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
E. Guzmán-Olea ◽  
V. H. Bermúdez-Morales ◽  
O. Peralta-Zaragoza ◽  
K. Torres-Poveda ◽  
V. Madrid-Marina
Keyword(s):  
Immune Response ◽  
Molecular Mechanisms ◽  
Immune Escape ◽  
Immune Surveillance ◽  
Hpv Infection ◽  
Etiologic Agent ◽  
Molecular Therapy ◽  
Cervical Lesions ◽  
Tumor Immune Escape ◽  
Joint Influence

Persistent infection with high-risk HPV is the etiologic agent associated with the development of cervical cancer (CC) development. However, environmental, social, epidemiological, genetic, and host factors may have a joint influence on the risk of disease progression. Cervical lesions caused by HPV infection can be removed naturally by the host immune response and only a small percentage may progress to cancer; thus, the immune response is essential for the control of precursor lesions and CC. We present a review of recent research on the molecular mechanisms that allow HPV-infected cells to evade immune surveillance and potential targets of molecular therapy to inhibit tumor immune escape.

scholarly journals Linking Tumor Microenvironment to Plasticity of Cancer Stem Cells: Mechanisms and Application in Cancer Therapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaobo Zheng ◽  
Chune Yu ◽  
Mingqing Xu
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Tumor Microenvironment ◽  
Cancer Stem Cells ◽  
Cancer Progression ◽  
Immune Escape ◽  
Underlying Mechanisms ◽  
Novel Therapeutic Strategies ◽  
And Function ◽  
The Relationship

Cancer stem cells (CSCs) are a minority subset of cancer cells that can drive tumor initiation, promote tumor progression, and induce drug resistance. CSCs are difficult to eliminate by conventional therapies and eventually mediate tumor relapse and metastasis. Moreover, recent studies have shown that CSCs display plasticity that renders them to alter their phenotype and function. Consequently, the varied phenotypes result in varied tumorigenesis, dissemination, and drug-resistance potential, thereby adding to the complexity of tumor heterogeneity and further challenging clinical management of cancers. In recent years, tumor microenvironment (TME) has become a hotspot in cancer research owing to its successful application in clinical tumor immunotherapy. Notably, emerging evidence shows that the TME is involved in regulating CSC plasticity. TME can activate stemness pathways and promote immune escape through cytokines and exosomes secreted by immune cells or stromal cells, thereby inducing non-CSCs to acquire CSC properties and increasing CSC plasticity. However, the relationship between TME and plasticity of CSCs remains poorly understood. In this review, we discuss the emerging investigations on TME and CSC plasticity to illustrate the underlying mechanisms and potential implications in suppressing cancer progression and drug resistance. We consider that this review can help develop novel therapeutic strategies by taking into account the interlink between TME and CSC plasticity.

scholarly journals Building neuromuscular junctions in vitro

Development ◽  
2020 ◽  
Vol 147 (22) ◽  
pp. dev193920
Author(s):  
Susie Barbeau ◽  
Julie Tahraoui-Bories ◽  
Claire Legay ◽  
Cécile Martinat
Keyword(s):  
Human Disease ◽  
Molecular Mechanisms ◽  
Neuromuscular Junctions ◽  
Ex Vivo ◽  
Culture Methods ◽  
Recent Developments ◽  
Chemical Synapses ◽  
And Function

ABSTRACTThe neuromuscular junction (NMJ) has been the model of choice to understand the principles of communication at chemical synapses. Following groundbreaking experiments carried out over 60 years ago, many studies have focused on the molecular mechanisms underlying the development and physiology of these synapses. This Review summarizes the progress made to date towards obtaining faithful models of NMJs in vitro. We provide a historical approach discussing initial experiments investigating NMJ development and function from Xenopus to mice, the creation of chimeric co-cultures, in vivo approaches and co-culture methods from ex vivo and in vitro derived cells, as well as the most recent developments to generate human NMJs. We discuss the benefits of these techniques and the challenges to be addressed in the future for promoting our understanding of development and human disease.

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