Emodin Administration Depolarizes Tumor Associated M2‐Type Macrophages in the Colorectal Cancer Tumor Microenvironment

Colorectal cancer (CRC) is the third most common malignancy and the second most common cause of cancer-related mortality worldwide. A total of 20% of CRC patients present with distant metastases, most frequently to the liver and lung. In the primary tumor, as well as at each metastatic site, the cellular components of the tumor microenvironment (TME) contribute to tumor engraftment and metastasis. These include immune cells (macrophages, neutrophils, T lymphocytes, and dendritic cells) and stromal cells (cancer-associated fibroblasts and endothelial cells). In this review, we highlight how the TME influences tumor progression and invasion at the primary site and its function in fostering metastatic niches in the liver and lungs. We also discuss emerging clinical strategies to target the CRC TME.

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TNF-alpha Induces Pro-Inflammatory Factors in Colorectal Cancer Microenvironment

Medical Science and Discovery ◽

10.36472/msd.v7i4.368 ◽

2020 ◽

Vol 7 (4) ◽

pp. 466-469

Author(s):

Ahu Pakdemirli ◽

Gizem Calibasi Kocal

Keyword(s):

Colorectal Cancer ◽

Tumor Microenvironment ◽

Cancer Cells ◽

Interleukin 6 ◽

Interleukin 8 ◽

Soluble Factors ◽

Tnf Α ◽

Colorectal Cancer Cells ◽

Cancer Tumor ◽

Cellular Components

Objective: The tumor microenvironment has a crucial role in organizing cancer malignancy, progression, drug resistance and survival. It consists of cellular and non-cellular components. These non-cellular components such as cytokines, extracellular matrix, growth factors and metabolites are responsible for shifting the action from pro-cancer to anti-cancer effects. Twenty percent of all cancers occur in association with chronic inflammation via cytokines. Even cancers that are not caused by chronic inflammation, present high levels of cytokine expression pattern in their tumor microenvironment. Tumor necrosis factor-alpha (TNF-α) and some interleukins are characterized as pro-tumorigenic cytokines and they were involved in cancer by presenting their ability to activate the oncogenic transcription factors. The aim of this study is to evaluate the remodeling of colorectal cancer tumor microenvironment by TNF-α. Material and Methods: TNF-α (5ng/ml) was applied to HT-29 colorectal cancer cells, then human soluble factors were determined by using Human Cytokine Group 1, 8 plex Panel (Bio-Rad Laboratories Inc. USA) and Magpix Luminex instrument and xPONENT software (version 4.2, Luminex Corp, Austin, Texas, US). The results were normalized to total protein concentration estimated via Bradford assay. Results: Current research highlights the effect of TNF-α on the tumor microenvironment. Interleukin-6 and interleukin -8 soluble factors were higher in TNF-α treated colorectal cancer cells when compared with untreated control group. Conclusion: The results of the study show that TNF-α is responsible for elevating the levels of interleukin-6 and interleukin-8, which are associated with inflammation in the tumor microenvironment. Key words: Colorectal Cancer, Tumor Microenvironment, Cytokines, TNF-α, Interleukin-6, interleukin -8

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Immune Landscape of Colorectal Cancer Tumor Microenvironment from Different Primary Tumor Location

Frontiers in Immunology ◽

10.3389/fimmu.2018.01578 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 38

Author(s):

Longhui Zhang ◽

Yuetao Zhao ◽

Ying Dai ◽

Jia-Nan Cheng ◽

Zhihua Gong ◽

...

Keyword(s):

Colorectal Cancer ◽

Tumor Microenvironment ◽

Primary Tumor ◽

Tumor Location ◽

Primary Tumor Location ◽

Cancer Tumor

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The Expression of Immune Checkpoint Receptors and Ligands in the Colorectal Cancer Tumor Microenvironment

Anticancer Research ◽

10.21873/anticanres.15303 ◽

2021 ◽

Vol 41 (10) ◽

pp. 4895-4905

Author(s):

PRAJWAL NEUPANE ◽

KOSAKU MIMURA ◽

SHOTARO NAKAJIMA ◽

HIROKAZU OKAYAMA ◽

MISATO ITO ◽

...

Keyword(s):

Colorectal Cancer ◽

Tumor Microenvironment ◽

Immune Checkpoint ◽

Cancer Tumor ◽

Checkpoint Receptors

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Regulation of the Prostate Cancer Tumor Microenvironment

10.21236/ada601302 ◽

2014 ◽

Author(s):

Arnold I. Chin

Keyword(s):

Prostate Cancer ◽

Tumor Microenvironment ◽

Cancer Tumor

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Role of Regulatory Oncogenic or Tumor Suppressor miRNAs of PI3K/AKT Signaling Axis in the Pathogenesis of Colorectal Cancer

Current Pharmaceutical Design ◽

10.2174/1381612825666190110151957 ◽

2019 ◽

Vol 24 (39) ◽

pp. 4605-4610 ◽

Cited By ~ 7

Author(s):

Atena Soleimani ◽

Farzad Rahmani ◽

Gordon A. Ferns ◽

Mikhail Ryzhikov ◽

Amir Avan ◽

...

Keyword(s):

Colorectal Cancer ◽

Tumor Suppressor ◽

Current Knowledge ◽

Akt Signaling ◽

Tumor Tissues ◽

Radio Therapy ◽

Signaling Axis ◽

Cancer Tumor ◽

Novel Biomarkers

Colorectal cancer (CRC) is the leading cause of cancer death worldwide and its incidence is increasing. In most patients with CRC, the PI3K/AKT signaling axis is over-activated. Regulatory oncogenic or tumor suppressor microRNAs (miRNAs) for PI3K/AKT signaling regulate cell proliferation, migration, invasion, angiogenesis, as well as resistance to chemo-/radio-therapy in colorectal cancer tumor tissues. Thus, regulatory miRNAs of PI3K/AKT/mTOR signaling represent novel biomarkers for new patient diagnosis and obtaining clinically invaluable information from post-treatment CRC patients for improving therapeutic strategies. This review summarizes the current knowledge of miRNAs’ regulatory roles of PI3K/AKT signaling in CRC pathogenesis.

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A tumor microenvironment-specific gene expression signature predicts chemotherapy resistance in colorectal cancer patients

npj Precision Oncology ◽

10.1038/s41698-021-00142-x ◽

2021 ◽

Vol 5 (1) ◽

Author(s):

Xiaoqiang Zhu ◽

Xianglong Tian ◽

Linhua Ji ◽

Xinyu Zhang ◽

Yingying Cao ◽

...

Keyword(s):

Colorectal Cancer ◽

Tumor Microenvironment ◽

Drug Sensitivity ◽

Chemotherapy Resistance ◽

Gene Expression Signature ◽

Prediction Algorithm ◽

Specific Gene ◽

Chemotherapy Response ◽

Rna Seq ◽

Mesenchymal Transition

AbstractStudies have shown that tumor microenvironment (TME) might affect drug sensitivity and the classification of colorectal cancer (CRC). Using TME-specific gene signature to identify CRC subtypes with distinctive clinical relevance has not yet been tested. A total of 18 “bulk” RNA-seq datasets (total n = 2269) and four single-cell RNA-seq datasets were included in this study. We constructed a “Signature associated with FOLFIRI resistant and Microenvironment” (SFM) that could discriminate both TME and drug sensitivity. Further, SFM subtypes were identified using K-means clustering and verified in three independent cohorts. Nearest template prediction algorithm was used to predict drug response. TME estimation was performed by CIBERSORT and microenvironment cell populations-counter (MCP-counter) methods. We identified six SFM subtypes based on SFM signature that discriminated both TME and drug sensitivity. The SFM subtypes were associated with distinct clinicopathological, molecular and phenotypic characteristics, specific enrichments of gene signatures, signaling pathways, prognosis, gut microbiome patterns, and tumor lymphocytes infiltration. Among them, SFM-C and -F were immune suppressive. SFM-F had higher stromal fraction with epithelial-to-mesenchymal transition phenotype, while SFM-C was characterized as microsatellite instability phenotype which was responsive to immunotherapy. SFM-D, -E, and -F were sensitive to FOLFIRI and FOLFOX, while SFM-A, -B, and -C were responsive to EGFR inhibitors. Finally, SFM subtypes had strong prognostic value in which SFM-E and -F had worse survival than other subtypes. SFM subtypes enable the stratification of CRC with potential chemotherapy response thereby providing more precise therapeutic options for these patients.

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The Relationship Between Tumor Budding, Tumor Microenvironment, and Survival in Patients with Primary Operable Colorectal Cancer

Annals of Surgical Oncology ◽

10.1245/s10434-019-07931-6 ◽

2019 ◽

Vol 26 (13) ◽

pp. 4397-4404 ◽

Cited By ~ 10

Author(s):

Hester C. van Wyk ◽

Antonia Roseweir ◽

Peter Alexander ◽

James H. Park ◽

Paul G. Horgan ◽

...

Keyword(s):

Colorectal Cancer ◽

Tumor Microenvironment ◽

Evaluation Method ◽

Venous Invasion ◽

Staging System ◽

Consensus Conference ◽

Tumor Budding ◽

Inflammatory Cell Infiltrate ◽

Cancer Specific Survival ◽

The Relationship

Abstract Background Tumor budding is an independent prognostic factor in colorectal cancer (CRC) and has recently been well-defined by the International Tumour Budding Consensus Conference (ITBCC). Objective The aim of the present study was to use the ITBCC budding evaluation method to examine the relationship between tumor budding, tumor factors, tumor microenvironment, and survival in patients with primary operable CRC. Methods Hematoxylin and eosin-stained slides of 952 CRC patients diagnosed between 1997 and 2007 were evaluated for tumor budding according to the ITBCC criteria. The tumor microenvironment was evaluated using tumor stroma percentage (TSP) and Klintrup–Makinen (KM) grade to assess the tumor inflammatory cell infiltrate. Results High budding (n = 268, 28%) was significantly associated with TNM stage (p < 0.001), competent mismatch repair (MMR; p < 0.05), venous invasion (p < 0.001), weak KM grade (p < 0.001), high TSP (p < 0.001), and reduced cancer-specific survival (CSS) (hazard ratio 8.68, 95% confidence interval 6.30–11.97; p < 0.001). Tumor budding effectively stratifies CSS stage T1 through to T4 (all p < 0.05) independent of associated factors. Conclusions Tumor budding effectively stratifies patients’ survival in primary operable CRC independent of other phenotypic features. In particular, the combination of T stage and budding should form the basis of a new staging system for primary operable CRC.

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