Tumor microenvironment, immune response and post-radiotherapy tumor clearance

Koukourakis, Michael I.; Giatromanolaki, Alexandra

doi:10.1007/s12094-020-02378-8

“…The immune system can detect and eliminate tumor cells [38,39]. Nonetheless, the tumor microenvironment could interact with this immunotherapy reaction by blocking various checkpoints through which the therapy operates [40]. Regulation of NK cells and tumor antigen-specific T cells is a key step that must take place for an antitumor immune response [41].…”

Section: Discussionmentioning

confidence: 99%

A Hypoxia Gene-Based Signature to Predict the Survival and Affect the Tumor Immune Microenvironment of Osteosarcoma in Children

Jiang

¹

,

Miao

²

,

Zhang

³

et al. 2021

Journal of Immunology Research

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Osteosarcoma is a quickly developing, malignant cancer of the bone, which is associated with a bad prognosis. In osteosarcoma, hypoxia promotes the malignant phenotype, which results in a cascade of immunosuppressive processes, poor prognosis, and a high risk of metastasis. Nonetheless, additional methodologies for the study of hyperoxia in the tumor microenvironment also need more analysis. We obtained 88 children patients with osteosarcoma from the Therapeutically Applicable Research to Generate Effective Treatment (TARGET) database and 53 children patients with RNA sequence and clinicopathological data from the Gene Expression Omnibus (GEO). We developed a four-gene signature related to hypoxia to reflect the immune microenvironment in osteosarcoma that predicts survival. A high-risk score indicated a poor prognosis and immunosuppressive microenvironment. The presence of the four-gene signature related to hypoxia was correlated with clinical and molecular features and was an important prognostic predictor for pediatric osteosarcoma patients. In summary, we established and validated a four-gene signature related to hypoxia to forecast recovery and presented an independent prognostic predictor representing overall immune response strength within the osteosarcoma microenvironment.

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“…This procedure is a part of treatment modalities of colorectal cancer nowadays that make adjuvant therapy more productive and improve the length of survival [ 95 ]. The TME is the main obstacle for the efficacy of adjuvant therapy, as impaired blood flow of growing tumor leads to hypoxia, acidity, and reduced accessibility of any drug [ 96 , 97 ]. Overcoming microenvironment-related resistance may have a fundamental impact on treatment efficacy and patient outcome [ 97 ].…”

Section: Discussionmentioning

confidence: 99%

Improvement in Redox Homeostasis after Cytoreductive Surgery in Colorectal Adenocarcinoma

Salehi

¹

,

Mirmiranpour

²

,

Rabizadeh

³

et al. 2021

Oxidative Medicine and Cellular Longevity

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Colorectal cancer (CRC) as one the most common cancer type is associated with oxidative stress. Surgery is the only curative modality for early-stage CRC. The aim of this study was to evaluate the oxidative damage biomarkers as well as enzymatic and nonenzymatic antioxidants in patients with CRC before and after tumor resection and in healthy controls. 60 patients with stage I/II colorectal adenocarcinoma and 43 healthy controls were recruited in this study. We measured plasma levels of oxidative damage biomarkers, including advanced oxidation protein products (AOPP), advanced glycation end products (AGEs), malondialdehyde (MDA), and oxidized low-density lipoprotein (ox-LDL) at baseline and after tumor removal. We also evaluated the plasma activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) as enzymatic antioxidants and the ferric reducing antioxidant power (FRAP) assay for nonenzymatic antioxidant capacity. Patients with CRC had significantly higher AGE, AOPP, MDA, and ox-LDL and also FRAP levels and higher SOD and GPx and lower CAT activity levels compared to healthy controls ( p < 0.05 ). We did not observe any statistically significant correlation between redox biomarkers and the size and stage of the tumor. AGEs ( 72.49 ± 4.7 vs. 67.93 ± 8.8 , p < 0.001 ), AOPP ( 137.64 ± 21.9 vs. 119.08 ± 33.1 , p < 0.001 ), MDA ( 3.56 ± 0.30 vs. 3.05 ± 0.33 , p < 0.001 ), and ox-LDL ( 19.78 ± 0.97 vs. 16.94 ± 1.02 , p < 0.001 ) concentrations reduced significantly after tumor removal. The largest effect sizes were found in ox-LDL ( d = − 2.853 , 95% CI 2.50-3.19) and MDA ( d = − 1.617 , 95% CI 0.43-0.57). Serum FRAP levels ( 1097.5 ± 156.7 vs. 1239.3 ± 290 , p < 0.001 ) and CAT ( 2.34 ± 0.34 vs. 2.63 ± 0.38 , p < 0.001 ), GPx ( 102.37 ± 6.58 vs. 108.03 ± 6.95 , p < 0.001 ), and SOD ( 5.13 ± 0.39 vs. 5.53 ± 0.31 , p < 0.001 ) activity levels increased significantly after surgery. The largest effect sizes among antioxidants were seen in SOD ( d = 1.135 , 95% CI 0.46-0.34) and GPx ( d = 0.836 , 95% CI 0.35-0.23). This study indicated that patients with colorectal cancer had higher levels of oxidative stress and antioxidant activity compared to healthy controls. After surgical resection of tumor, we observed a substantial improvement in redox homeostasis.

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“…For example, intratumoral hypoxia and acidity strongly prevent proliferation and the cytolytic activity of lymphocytes and monocytes. Moreover, conditions related to amino acid metabolism (such as arginine and tryptophan) or ATP transformation to adenosine adversely affect the survival and proliferation of cytotoxic immune cells in tumors [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Prognostic and Predictive Relevance of Tumor-Infiltrating Lymphocytes in Squamous Cell Head–Neck Cancer Patients Treated with Radical Radiotherapy/Chemo-Radiotherapy

Koukourakis

¹

,

Gkegka

²

,

Xanthopoulou

³

et al. 2022

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Microenvironmental conditions control the entrance and thriving of cytotoxic lymphocytes in tumors, allowing or preventing immune-mediated cancer cell death. We investigated the role of tumor-infiltrating lymphocyte (TIL) density in the outcome of radiotherapy in a series of squamous cell head–neck tumors (HNSCC). Moreover, we assessed the link between markers of hypoxia and TIL density. One-hundred twenty-one patients with HNSCC treated prospectively with radical radiotherapy/chemo-radiotherapy were analyzed. The assessment of TIL density was performed on hematoxylin and eosin biopsy sections before radiotherapy. TIL density ranged from 0.8 to 150 lymphocytes per ×40 optical field (median 27.5). Using the median value, patients were grouped into two categories of low and high TIL density. Early T-stage tumors had a significantly higher TIL density (p < 0.003), but we found no association with N-stage. Overexpression of HIF1α, HIF2α, and CA9 was significantly linked with poor infiltration by TILs (p < 0.03). A significant association of high TIL density with better disease-specific overall survival and improved locoregional relapse-free survival was noted (p = 0.008 and 0.02, respectively), which was also confirmed in multivariate analysis. It is concluded that HNSCC phenotypes that allow for the intratumoral accumulation of lymphocytes have a better outcome following radical radiotherapy/chemo-radiotherapy. Intratumoral-activated HIF- and CA9-related pathways characterize immunologically cold tumors and may be used as targets for therapeutic interventions.

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Tumor microenvironment, immune response and post-radiotherapy tumor clearance

Cited by 29 publications

References 61 publications

A Hypoxia Gene-Based Signature to Predict the Survival and Affect the Tumor Immune Microenvironment of Osteosarcoma in Children

A Hypoxia Gene-Based Signature to Predict the Survival and Affect the Tumor Immune Microenvironment of Osteosarcoma in Children

Improvement in Redox Homeostasis after Cytoreductive Surgery in Colorectal Adenocarcinoma

Prognostic and Predictive Relevance of Tumor-Infiltrating Lymphocytes in Squamous Cell Head–Neck Cancer Patients Treated with Radical Radiotherapy/Chemo-Radiotherapy

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