Characteristics of hypoxic tumor microenvironment in non-small cell lung cancer, involving molecular patterns and prognostic signature

Huang, Zhanghao; Wang, Shuo; Zhang, Haijian; Tang, Xin; Shi, Jiahai

doi:10.21037/tlcr-20-1314

Cited by 5 publications

(4 citation statements)

References 41 publications

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“…As evident from the table, every signature consists of its own set of genes, even if it was derived from the same tumor type, with minimal overlap with other signatures. The conclusions of most papers underscore the immunosuppressive power of hypoxia in bladder cancer ( 189 , 213 ), breast cancer ( 214 ), colorectal cancer (CRC) ( 191 , 216 , 217 ), head and neck squamous cell carcinoma ( 218 ), hepatocellular carcinoma (HCC) ( 221 – 223 ), lung cancer ( 195 , 225 , 226 ), melanoma ( 196 ), oral squamous cell carcinoma ( 227 ), osteosarcoma ( 229 ), ovarian carcinoma ( 230 ) and pancreatic ductal adenocarcinoma (PDAC) ( 197 , 231 ). In the case of bladder cancer, two other studies determined the presence of high infiltration of immune cells in the high-risk group and found positive correlations between immune score and the risk score ( 190 , 212 ).…”

Section: Unraveling the Hypoxia-immune Contexture In Silico...mentioning

confidence: 99%

The Effect of Hypoxia and Hypoxia-Associated Pathways in the Regulation of Antitumor Response: Friends or Foes?

et al. 2022

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Hypoxia is an environmental stressor that is instigated by low oxygen availability. It fuels the progression of solid tumors by driving tumor plasticity, heterogeneity, stemness and genomic instability. Hypoxia metabolically reprograms the tumor microenvironment (TME), adding insult to injury to the acidic, nutrient deprived and poorly vascularized conditions that act to dampen immune cell function. Through its impact on key cancer hallmarks and by creating a physical barrier conducive to tumor survival, hypoxia modulates tumor cell escape from the mounted immune response. The tumor cell-immune cell crosstalk in the context of a hypoxic TME tips the balance towards a cold and immunosuppressed microenvironment that is resistant to immune checkpoint inhibitors (ICI). Nonetheless, evidence is emerging that could make hypoxia an asset for improving response to ICI. Tackling the tumor immune contexture has taken on an in silico, digitalized approach with an increasing number of studies applying bioinformatics to deconvolute the cellular and non-cellular elements of the TME. Such approaches have additionally been combined with signature-based proxies of hypoxia to further dissect the turbulent hypoxia-immune relationship. In this review we will be highlighting the mechanisms by which hypoxia impacts immune cell functions and how that could translate to predicting response to immunotherapy in an era of machine learning and computational biology.

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Section: Unraveling the Hypoxia-immune Contexture In Silico...mentioning

confidence: 99%

The Effect of Hypoxia and Hypoxia-Associated Pathways in the Regulation of Antitumor Response: Friends or Foes?

et al. 2022

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“…Lung cancer is a highly hypoxic cancer type with two-times lower oxygen percentage in the tumor side in comparison to normal tissue. Hypoxia limits immune cell infiltration and conducts tumor surveillance [76]. It is also involved in tumor EMT stimulation and treatment-resistance, mainly in radiotherapy [77].…”

Section: Immunology Of Lung Cancer Tumormentioning

confidence: 99%

Clinical Application Perspectives of Lung Cancers 3D Tumor Microenvironment Models for In Vitro Cultures

Wieleba

Wojas‐Krawczyk

Krawczyk

et al. 2022

IJMS

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Despite the enormous progress and development of modern therapies, lung cancer remains one of the most common causes of death among men and women. The key element in the development of new anti-cancer drugs is proper planning of the preclinical research phase. The most adequate basic research exemplary for cancer study are 3D tumor microenvironment in vitro models, which allow us to avoid the use of animal models and ensure replicable culture condition. However, the question tormenting the scientist is how to choose the best tool for tumor microenvironment research, especially for extremely heterogenous lung cancer cases. In the presented review we are focused to explain the key factors of lung cancer biology, its microenvironment, and clinical gaps related to different therapies. The review summarized the most important strategies for in vitro culture models mimicking the tumor–tumor microenvironmental interaction, as well as all advantages and disadvantages were depicted. This knowledge could facilitate the right decision to designate proper pre-clinical in vitro study, based on available analytical tools and technical capabilities, to obtain more reliable and personalized results for faster introduction them into the future clinical trials.

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“…Hypoxia plays an important role in the cells-microenvironment including several tumors [35]. During deprivation of sufficient oxygen supply, cells cannot keep adequate antioxidant capability resulting in increased ROS levels [36].…”

Section: Hypoxia and Ros In Tumor Progressionmentioning

confidence: 99%

Comprehension of the Relationship between Autophagy and Reactive Oxygen Species for Superior Cancer Therapy with Histone Deacetylase Inhibitors

Ikeda

Nagase

Tsuji

et al. 2021

Oxygen

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Epigenetics contains various mechanisms by which cells employ to regulate the transcription of many DNAs. Histone acetylation is an obvious example of the epigenetic mechanism regulating the expression of several genes by changing chromatin accessibility. Histone deacetylases (HDACs) are a class of enzymes that play a critical role in the epigenetic regulation by deacetylation of histone proteins. Inhibitors of the histone deacetylase could result in hyperacetylation of histones, which eventually induce various cellular consequences such as generation of reactive oxygen species (ROS), activation of apoptotic pathways, and initiating autophagy. In particular, excessive levels of ROS have been proposed to contribute to the pathophysiology of various diseases including cancer. Cancers are, as it were, a class of redox diseases. Low levels of ROS are beneficial for cells, however, cancer cells generally have high levels of ROS, which makes them more susceptible than normal cells to the further increases of ROS levels. Cancer cells exhibit metabolic alterations for managing to sustain these oxidative stresses. There is a growing interest in the use of HDAC inhibitors as promising cancer therapeutics with potentiating the activity of established therapeutic applications. Therefore, it should be important to understand the underlying relationship between the regulation of HDACs, ROS production, and cancer cell biology.

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Characteristics of hypoxic tumor microenvironment in non-small cell lung cancer, involving molecular patterns and prognostic signature

Cited by 5 publications

References 41 publications

The Effect of Hypoxia and Hypoxia-Associated Pathways in the Regulation of Antitumor Response: Friends or Foes?

The Effect of Hypoxia and Hypoxia-Associated Pathways in the Regulation of Antitumor Response: Friends or Foes?

Clinical Application Perspectives of Lung Cancers 3D Tumor Microenvironment Models for In Vitro Cultures

Comprehension of the Relationship between Autophagy and Reactive Oxygen Species for Superior Cancer Therapy with Histone Deacetylase Inhibitors

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