scholarly journals Hypoxia and the Tumor Microenvironment

2021 ◽  
Vol 20 ◽  
pp. 153303382110363
Author(s):  
Yue Li ◽  
Long Zhao ◽  
Xiao-Feng Li
Keyword(s):  
Immune Response ◽  
Cell Proliferation ◽  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Poor Prognosis ◽  
Tumor Biology ◽  
Metastatic Potential ◽  
Tumor Detection ◽  
Tumor Aggressiveness

Hypoxia is an important feature of the tumor microenvironment, and is closely associated with cell proliferation, angiogenesis, metabolism and the tumor immune response. All these factors can further promote tumor progression, increase tumor aggressiveness, enhance tumor metastatic potential and lead to poor prognosis. In this review, these effects of hypoxia on tumor biology will be discussed, along with their significance for tumor detection and treatment.

scholarly journals Recruitment and Expansion of Tregs Cells in the Tumor Environment—How to Target Them?

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1850
Author(s):  
Justine Cinier ◽  
Margaux Hubert ◽  
Laurie Besson ◽  
Anthony Di Roio ◽  
Céline Rodriguez ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Poor Prognosis ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Major Function ◽  
Normal Tissues ◽  
Tumor Environment ◽  
Plastic Transformation

Regulatory T cells (Tregs) are present in a large majority of solid tumors and are mainly associated with a poor prognosis, as their major function is to inhibit the antitumor immune response contributing to immunosuppression. In this review, we will investigate the mechanisms involved in the recruitment, amplification and stability of Tregs in the tumor microenvironment (TME). We will also review the strategies currently developed to inhibit Tregs’ deleterious impact in the TME by either inhibiting their recruitment, blocking their expansion, favoring their plastic transformation into other CD4+ T-cell subsets, blocking their suppressive function or depleting them specifically in the TME to avoid severe deleterious effects associated with Treg neutralization/depletion in the periphery and normal tissues.

scholarly journals Tumor-associated macrophages: potential therapeutic strategies and future prospects in cancer

2021 ◽  
Vol 9 (1) ◽  
pp. e001341
Author(s):  
Chunxiao Li ◽  
Xiaofei Xu ◽  
Shuhua Wei ◽  
Ping Jiang ◽  
Lixiang Xue ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Poor Prognosis ◽  
Tumor Immunotherapy ◽  
Therapeutic Strategies ◽  
Preclinical Studies ◽  
Future Prospects ◽  
Tumor Associated Macrophages

Macrophages are the most important phagocytes in vivo. However, the tumor microenvironment can affect the function and polarization of macrophages and form tumor-associated macrophages (TAMs). Usually, the abundance of TAMs in tumors is closely associated with poor prognosis. Preclinical studies have identified important pathways regulating the infiltration and polarization of TAMs during tumor progression. Furthermore, potential therapeutic strategies targeting TAMs in tumors have been studied, including inhibition of macrophage recruitment to tumors, functional repolarization of TAMs toward an antitumor phenotype, and other therapeutic strategies that elicit macrophage-mediated extracellular phagocytosis and intracellular destruction of cancer cells. Therefore, with the increasing impact of tumor immunotherapy, new antitumor strategies to target TAMs are now being discussed.

scholarly journals CAFs Interacting With TAMs in Tumor Microenvironment to Enhance Tumorigenesis and Immune Evasion

2021 ◽  
Vol 11 ◽  
Author(s):  
Gurcan Gunaydin
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Tumor Cells ◽  
Immune Evasion ◽  
Poor Prognosis ◽  
Cancer Associated Fibroblasts ◽  
Mutual Relationship ◽  
Complex Interplay ◽  
Tumor Immune Evasion ◽  
Mechanisms Of Carcinogenesis

Cancer associated fibroblasts (CAFs) and tumor associated macrophages (TAMs) are among the most important and abundant players of the tumor microenvironment. CAFs as well as TAMs are known to play pivotal supportive roles in tumor growth and progression. The number of CAF or TAM cells is mostly correlated with poor prognosis. Both CAFs and TAMs are in a reciprocal communication with the tumor cells in the tumor milieu. In addition to such interactions, CAFs and TAMs are also involved in a dynamic and reciprocal interrelationship with each other. Both CAFs and TAMs are capable of altering each other’s functions. Here, the current understanding of the distinct mechanisms about the complex interplay between CAFs and TAMs are summarized. In addition, the consequences of such a mutual relationship especially for tumor progression and tumor immune evasion are highlighted, focusing on the synergistic pleiotropic effects. CAFs and TAMs are crucial components of the tumor microenvironment; thus, they may prove to be potential therapeutic targets. A better understanding of the tri-directional interactions of CAFs, TAMs and cancer cells in terms of tumor progression will pave the way for the identification of novel theranostic cues in order to better target the crucial mechanisms of carcinogenesis.

scholarly journals The Distinct Roles of CXCR3 Variants and Their Ligands in the Tumor Microenvironment

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 613 ◽  
Author(s):  
Reynders ◽  
Abboud ◽  
Baragli ◽  
Noman ◽  
Rogister ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Cancer Progression ◽  
Chemokine Receptor ◽  
Inflammatory Diseases ◽  
Multiple Roles ◽  
Leukocyte Trafficking ◽  
Tumor Bed ◽  
Normal Functions

First thought to orchestrate exclusively leukocyte trafficking, chemokines are now acknowledged for their multiple roles in the regulation of cell proliferation, differentiation, and survival. Dysregulation of their normal functions contributes to various pathologies, including inflammatory diseases and cancer. The two chemokine receptor 3 variants CXCR3-A and CXCR3-B, together with their cognate chemokines (CXCL11, CXCL10, CXCL9, CXCL4, and CXCL4L1), are involved in the control but also in the development of many tumors. CXCR3-A drives the infiltration of leukocytes to the tumor bed to modulate tumor progression (paracrine axis). Conversely, tumor-driven changes in the expression of the CXCR3 variants and their ligands promote cancer progression (autocrine axis). This review summarizes the anti- and pro-tumoral activities of the CXCR3 variants and their associated chemokines with a focus on the understanding of their distinct biological roles in the tumor microenvironment.

scholarly journals Heterogeneity of tumor microenvironment is associated with clinical prognosis of non-clear cell renal cell carcinoma: a single-cell genomics study

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Wen-jin Chen ◽  
Hao Cao ◽  
Jian-wei Cao ◽  
Li Zuo ◽  
Fa-jun Qu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Cell Carcinoma ◽  
Cd8 T Cells ◽  
Renal Cell ◽  
Poor Prognosis ◽  
Tumor Biology ◽  
Cell Types ◽  
Duct Carcinoma

AbstractNon-clear renal cell carcinomas (nccRCCs) are less frequent in kidney cancer with histopathological heterogeneity. A better understanding of the tumor biology of nccRCC can provide more effective treatment paradigms for different subtypes. To reveal the heterogeneity of tumor microenvironment (TME) in nccRCC, we performed 10x sing-cell genomics on tumor and normal tissues from patients with papillary renal cell carcinoma (pRCC), chromophobe RCC (chrRCC), collecting duct carcinoma (CDRCC) and sarcomatoid RCC (sarRCC). 15 tissue samples were finally included. 34561 cells were identified as 16 major cell clusters with 34 cell subtypes. Our study presented the sing-cell landscape for four types of nccRCC, and demonstrated that CD8+ T cells exhaustion, tumor-associated macrophages (TAMs) and sarcomatoid process were the pivotal factors in immunosuppression of nccRCC tissues and were closely correlated with poor prognosis. Abnormal metabolic patterns were present in both cancer cells and tumor-infiltrating stromal cells, such as fibroblasts and endothelial cells. Combined with CIBERSORTx tool, the expression data of bulk RNA-seq from TCGA were labeled with cell types of our sing-cell data. Calculation of the relative abundance of cell types revealed that greater proportion of exhausted CD8+ T cells, TAMs and sarRCC derived cells were correlated with poor prognosis in the cohort of 274 nccRCC patients. To the best of our knowledge, this is the first study that provides a more comprehensive sight about the heterogeneity and tumor biology of nccRCC, which may potentially facilitate the development of more effective therapies for nccRCC.

scholarly journals The CC and CXC chemokines: major regulators of tumor progression and the tumor microenvironment

2020 ◽  
Vol 318 (3) ◽  
pp. C542-C554 ◽  
Author(s):  
Andreas Bikfalvi ◽  
Clotilde Billottet
Keyword(s):  
Cell Proliferation ◽  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Tumor Cells ◽  
Tumor Immunity ◽  
Chemokine Receptor ◽  
Immune Cells ◽  
Immune Dysfunction ◽  
Mechanisms Of Action ◽  
Migration Of Cells

Chemokines are a family of soluble cytokines that act as chemoattractants to guide the migration of cells, in particular of immune cells. However, chemokines are also involved in cell proliferation, differentiation, and survival. Chemokines are associated with a variety of human diseases including chronic inflammation, immune dysfunction, cancer, and metastasis. This review discusses the expression of CC and CXC chemokines in the tumor microenvironment and their supportive and inhibitory roles in tumor progression, angiogenesis, metastasis, and tumor immunity. We also specially focus on the diverse roles of CXC chemokines (CXCL9–11, CXCL4 and its variant CXCL4L1) and their two chemokine receptor CXCR3 isoforms, CXCR3-A and CXCR3-B. These two distinct isoforms have divergent roles in tumors, either promoting (CXCR3-A) or inhibiting (CXCR3-B) tumor progression. Their effects are mediated not only directly in tumor cells but also indirectly via the regulation of angiogenesis and tumor immunity. A full comprehension of their mechanisms of action is critical to further validate these chemokines and their receptors as biomarkers or therapeutic targets in cancer.

scholarly journals Targeting the Tumor Microenvironment: An Unexplored Strategy for Mutant KRAS Tumors

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2010 ◽  
Author(s):  
Patrícia Dias Carvalho ◽  
Ana Luísa Machado ◽  
Flávia Martins ◽  
Raquel Seruca ◽  
Sérgia Velho
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Expression Profile ◽  
Poor Prognosis ◽  
Therapeutic Option ◽  
Metastatic Potential ◽  
Therapeutic Strategies ◽  
Current Evidence ◽  
Downstream Effectors

Current evidence strongly suggests that cancer cells depend on the microenvironment in order to thrive. In fact, signals from the surrounding tumor microenvironment are crucial for cancer cells´ aggressiveness, altering their expression profile and favoring their metastatic potential. As such, targeting the tumor microenvironment to impair cancer progression became an attractive therapeutic option. Interestingly, it has been shown that oncogenic KRAS signaling promotes a pro-tumorigenic microenvironment, and the associated crosstalk alters the expression profile of cancer cells. These findings award KRAS a key role in controlling the interactions between cancer cells and the microenvironment, granting cancer a poor prognosis. Given the lack of effective approaches to target KRAS itself or its downstream effectors in the clinic, exploring such interactions may open new perspectives on possible therapeutic strategies to hinder mutant KRAS tumors. This review highlights those communications and their implications for the development of effective therapies or to provide insights regarding response to existing regimens.

scholarly journals Low miR-1231 expression predicts poor prognosis in non-small cell lung cancer and accelerates cell proliferation, migration and invasion

2020 ◽  
Author(s):  
Lina Zhu ◽  
Chu Zhang ◽  
Hui Yu ◽  
Lirong Zhu
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Tumor Progression ◽  
Poor Prognosis ◽  
Biological Function ◽  
Small Cell ◽  
Nsclc Cell ◽  
Migration And Invasion ◽  
Small Cell Lung

Abstract Background MicroRNAs (miRNAs) have been confirmed to be involved in the tumor progression of various cancer types. This study aimed to assess the prognostic significance and biological function of miR-1231 in patients with non-small cell lung cancer (NSCLC). Methods The expression of miR-1231 was estimated using quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan-Meier survival curves and Cox regression analysis were used to evaluate the prognosis value of miR-1231 in patients with NSCLC. Cell experiments were performed to assess the biological function of miR-1231 in the tumor progression. Results In this study, we found that miR-1231 was an important tumor suppressor with significantly low expression in NSCLC tissues and cell lines compared with normal controls (all P < 0.001). MiR-1231 expression was significantly associated with tumor size (P = 0.037), lymph node metastasis (P = 0.001) and TNM stages (P = 0.001). Furthermore, the patients with low miR-1231 expression had shorter survival time than those with high miR-1231 expression (log-rank P = 0.010). In addition, miR-1231 was found to serve as an independent prognostic biomarker for the patients. The results of cell experiments indicated that miR-1231 downregulation could markedly promote NSCLC cell proliferation, migration and invasion, while miR-1231 overexpression could markedly inhibit NSCLC cell proliferation, migration and invasion. Conclusion All the data revealed that a downregulated expression of miR-1231 predicts the poor prognosis of NSCLC and promotes the tumor cell proliferation, migration and invasion. Therefore, we considered that miR-1231 may serve as a therapeutic target for NSCLC treatment.

scholarly journals m6A Regulator-Associated Modification Patterns and Immune Infiltration of the Tumor Microenvironment in Hepatocarcinoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Jianhao Li ◽  
Weiwei Wang ◽  
Yubing Zhou ◽  
Liwen Liu ◽  
Guizhen Zhang ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Clinical Features ◽  
Poor Prognosis ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
T Cell Infiltration ◽  
The Relationship

Background: Immunotherapy elicits durable responses in many tumors. Nevertheless, the positive response to immunotherapy always depends on the dynamic interactions between the tumor cells and infiltrating lymphocytes in the tumor microenvironment (TME). Currently, the application of immunotherapy in hepatocellular carcinoma (HCC) has achieved limited success. The ectopic modification of N6-methyladenosine (m6A) is a common feature in multiple tumors. However, the relationship between m6A modification with HCC clinical features, prognosis, immune cell infiltration, and immunotherapy efficacy remains unclear.Materials and Methods: Here, we comprehensively evaluated m6A modification clusters based on 22 m6A regulators and systematically explored the relationship between m6A modification with tumor progression, prognosis, and immune cell infiltration characteristics. The m6Ascore was calculated by principal component analysis to quantify the m6A modifications of individual patients. Key regulators involved in immunoregulation in HCC were identified using immunohistochemistry and immunofluorescence.Results: Three distinct m6A modification clusters were identified. The m6A clusters were significantly associated with clinical features, prognosis, and immune cell infiltration. The three clusters were highly consistent with the three tumor immune phenotypes, i.e., immune-excluded, immune-inflamed, and immune-desert. Comprehensive bioinformatics analysis revealed that high m6Ascore was closely associated with tumor progression, poor prognosis, and immunotherapy non-response. m6A regulators were dysregulated in HCC tissues. Hence, they play a role as predictors of poor prognosis. Tissue microarray demonstrated that overexpressed YTHDF1 was associated with low CD3+ and CD8+ T cell infiltration in HCC.Conclusion: Our findings demonstrate that m6A modification patterns play a crucial role in the tumor immune microenvironment and the prognosis of HCC. High YTHDF1 expression is closely associated with low CD3+ and CD8+ T cell infiltration in HCC.

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