Prognostic Impact of Tumor Immune Microenvironment and Systemic Inflammatory Markers in Colorectal Cancer

2020 ◽  
Vol 46 (2) ◽  
pp. e87
Author(s):  
Sang-Jeon Lee ◽  
Ji Won Park ◽  
Gyeong Hoon Kang ◽  
Jung Ho Kim ◽  
Jeong Mo Bae ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Markers ◽  
Prognostic Impact ◽  
Immune Microenvironment ◽  
Tumor Immune Microenvironment

151 - Colonic Bacteria and the Tumor Immune Microenvironment of Colorectal Cancer Patients

2018 ◽  
Vol 154 (6) ◽  
pp. S-41
Author(s):  
Jada C. Domingue ◽  
Nicolas Llosa ◽  
James White ◽  
Julia L. Drewes ◽  
Christine Craig ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Immune Microenvironment ◽  
Colonic Bacteria ◽  
Tumor Immune Microenvironment ◽  
Colorectal Cancer Patients

Comparing of pan-cancer tumor immune microenvironment.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15100-e15100
Author(s):  
Jiaan Ye ◽  
Longgang Cui ◽  
Xiaochen Zhao ◽  
Guanghui Lan
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
Natural Killer Cell ◽  
Natural Killer ◽  
Cancer Patients ◽  
Killer Cell ◽  
Immune Microenvironment ◽  
Hepatobiliary Cancer ◽  
Tumor Immune Microenvironment ◽  
Pan Cancer

e15100 Background: Cancer treatment has entered the era of immune checkpoint inhibitors (ICI), but different tumors have different responses to ICI drugs. For example, non-small cell lung cancer and melanoma have higher response rates to ICIs than colorectal cancer and liver cancer patients. Previous studies have shown that tumor immune microenvironment have a great impact on the efficacy of ICI. Methods: This study retrospectively included pan-cancer patient specimens, using multiple fluorescent labeling immunohistochemistry to explore the differences in the immune microenvironment of different tumors. Shapiro-Wilk was used for normality test, and ANOVA or Kruskal Wallis test was used according to the results. Two-sided P < 0.05 was considered a significant difference. Results: The study included 308 patients, including 119 (38.6%) NSCLC patients, 72 (23.4%) Colorectal cancer patients, 51 (16.6%) Hepatobiliary cancer patients and 66 (21.4%) Others types of cancer patients. Among them, there was 192 (62.3%) Male, and 116 (37.7%) Female, and the median age was 57 (50-66). The proportion of CD8+ T cells and natural killer cell in tumor was statistically different. The proportion of CD8+ T cells in NSCLC, Colorectal cancer, Hepatobiliary cancer and others was 2.16%, 1%, 1.77% and 2.63%, p < 0.01; the proportion of natural killer cell was 16.44 %, 4.91%, 5.58% and 3.29%, p < 0.01. Conclusions: Different tumor types have different immune microenvironments. These results may provide valuable clues for future ICI trail design.

scholarly journals RNA N6-Methyladenosine Regulators Contribute to Tumor Immune Microenvironment and Have Clinical Prognostic Impact in Breast Cancer

2022 ◽  
Vol 12 ◽  
Author(s):  
Lan-Xin Mu ◽  
You-Cheng Shao ◽  
Lei Wei ◽  
Fang-Fang Chen ◽  
Jing-Wei Zhang
Keyword(s):  
Breast Cancer ◽  
Immune Cell ◽  
Risk Model ◽  
Cox Regression ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Prognostic Impact ◽  
Immune Microenvironment ◽  
Model Based ◽  
Tumor Immune Microenvironment

Purpose: This study aims to reveal the relationship between RNA N6-methyladenosine (m6A) regulators and tumor immune microenvironment (TME) in breast cancer, and to establish a risk model for predicting the occurrence and development of tumors.Patients and methods: In the present study, we respectively downloaded the transcriptome dataset of breast cancer from Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database to analyze the mutation characteristics of m6A regulators and their expression profile in different clinicopathological groups. Then we used the weighted correlation network analysis (WGCNA), the least absolute shrinkage and selection operator (LASSO), and cox regression to construct a risk prediction model based on m6A-associated hub genes. In addition, Immune infiltration analysis and gene set enrichment analysis (GSEA) was used to evaluate the immune cell context and the enriched gene sets among the subgroups.Results: Compared with adjacent normal tissue, differentially expressed 24 m6A regulators were identified in breast cancer. According to the expression features of m6A regulators above, we established two subgroups of breast cancer, which were also surprisingly distinguished by the feature of the immune microenvironment. The Model based on modification patterns of m6A regulators could predict the patient’s T stage and evaluate their prognosis. Besides, the low m6aRiskscore group presents an immune-activated phenotype as well as a lower tumor mutation load, and its 5-years survival rate was 90.5%, while that of the high m6ariskscore group was only 74.1%. Finally, the cohort confirmed that age (p &lt; 0.001) and m6aRiskscore (p &lt; 0.001) are both risk factors for breast cancer in the multivariate regression.Conclusion: The m6A regulators play an important role in the regulation of breast tumor immune microenvironment and is helpful to provide guidance for clinical immunotherapy.

Prognostic impact of tristetraprolin (TTP) and PTEN loss and assessment of associated immune infiltrates in localized prostate cancer (PrCa).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16601-e16601
Author(s):  
Anis Hamid ◽  
Lillian Werner ◽  
Ying Huang ◽  
Cecile Vicier ◽  
Katherine Morel ◽  
...  
Keyword(s):  
Tissue Microarrays ◽  
Wilcoxon Test ◽  
Rank Test ◽  
Prognostic Impact ◽  
Immune Microenvironment ◽  
Pten Loss ◽  
Immune Marker ◽  
Kaplan Meier ◽  
Tumor Immune Microenvironment ◽  
A Cell

e16601 Background: We previously showed that loss of PTEN by quantitative multiplex immunofluorescence (qIF) is associated with relapse after prostatectomy. Low expression of TTP, which modulates the NF-kB pathway and inflammation, is prognostic for lethal PrCa after surgery. We also showed, with this assay, that low CD8+ density is a poor prognostic marker. We hypothesized that co-loss of these independent cell signaling regulators leads to poorer outcomes, and low TTP is associated with a modified tumor immune microenvironment. Methods: qIF was performed on tissue microarrays from a cohort treated by radical prostatectomy (N = 128). PTEN and TTP expression intensity was measured continuously at a cell-by-cell level and summarized per patient using binary thresholds. Immune marker (CD3, CD8, PD-L1, PD-1, FOXP3) density (positive cells/area) was evaluated in glands and stroma. Median time to biochemical recurrence (BCR) and metastasis (MFS) was estimated using Kaplan Meier method and log rank test summarized associations between expression and time to event outcomes. Wilcoxon test assessed the association of biomarker status and immune marker density. Results: Of 128 patients with a median follow-up of 14.6 years, 67 (52%) had BCR. 102 had staining for PTEN, 103 for TTP and 86 for both. Key findings are detailed in Table. PTEN and TTP co-loss was associated with the shortest time to BCR and worst MFS. TTP-low tumors had an immune infiltrate deplete of CD8 (p = 0.0004) and PD-1 (p = 0.0001) expressing cells. No significant differences in immune markers were noted by PTEN status. Conclusions: Co-loss of regulators of inflammation and cell cycling is associated with incremental risk of relapse in localized PrCa. Loss of TTP is associated with a diminished effector T cell infiltrate and may be a modifier towards a ‘cold’ PrCa immune microenvironment. Table: Clinical outcomes by biomarker status [Table: see text]

scholarly journals Constructing Tumor Immune Microenvironment and Identifying the Immune-Related Prognostic Signatures in Colorectal Cancer Using Multi-omics Data

2021 ◽  
Author(s):  
Shuai Zhang ◽  
Jiali Lv ◽  
Bingbing Fan ◽  
Zhe Fan ◽  
Chunxia Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cross Validation ◽  
Cox Regression ◽  
Risk Group ◽  
The Cancer Genome Atlas ◽  
Omics Data ◽  
Epigenetic Alterations ◽  
Lasso Regression ◽  
Immune Microenvironment ◽  
Tumor Immune Microenvironment

ABSTRACTBackgroundThe tumor immune microenvironment (TIME) plays a key role in occurrence, progression and prognosis of colorectal cancer (CRC). However, the genetic and epigenetic alterations and potential mechanisms in the TIME of CRC are still unclear.MethodsWe investigated the immune-related differences in three types of genetic or epigenetic alterations (gene expression, somatic mutation, and DNA methylation) and considered the potential roles that these alterations have in the immune response and the immune-related biological processes by analyzing the multi-omics data from The Cancer Genome Atlas (TCGA) portal. Additionally, a four-step method based on LASSO regression and Cox regression was used to construct the prognostic prediction model. Cross validation was performed to validate the model.ResultsA total of 1,745 differentially expressed genes, 178 differentially mutated genes and 1,961 differentially methylation probes were identified between the high-immunity group and the low-immunity group. We retained 15 genetic and epigenetic variables after using LASSO regression and Cox regression. For the prognostic predictions on the TCGA profiles, the performance of the model with 1-year, 3-year, and 5-year areas under the curve (AUCs) equal to 0.861, 0.797, and 0.875. Finally, the overall risk score model was constructed based on genetic, epigenetic, demographic and clinical characteristics, which comprised 18 variables and achieved a high degree of accuracy on the 1-year (AUC = 0.865), 3-year (AUC = 0.839), and 5-year (AUC = 0.914) survival predictions. Kaplan-Meier survival analysis demonstrated that the overall survival of the high-risk group was significantly poorer compared with the low-risk group. Prognostic nomogram, calibration plot and cross validation showed excellent predictive performance.ConclusionsOur study provides a new clue to explore the TIME of CRC patients in genetic and epigenetic aspects. Meanwhile, the prognostic model also has clinical prognostic value and may provide new indicators for the treatment of CRC patients.

scholarly journals Bioinorganic hybrid bacteriophage for modulation of intestinal microbiota to remodel tumor-immune microenvironment against colorectal cancer

2020 ◽  
Vol 6 (20) ◽  
pp. eaba1590 ◽  
Author(s):  
Xue Dong ◽  
Pei Pan ◽  
Di-Wei Zheng ◽  
Peng Bao ◽  
Xuan Zeng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Checkpoint Inhibitors ◽  
Suppressor Cells ◽  
In Vivo Studies ◽  
Host Immune System ◽  
Immune Microenvironment ◽  
Phage Display Technology ◽  
Tumor Immune Microenvironment

Mounting evidence suggests that the gut microbiota contribute to colorectal cancer (CRC) tumorigenesis, in which the symbiotic Fusobacterium nucleatum (Fn) selectively increases immunosuppressive myeloid-derived suppressor cells (MDSCs) to hamper the host’s anticancer immune response. Here, a specifically Fn-binding M13 phage was screened by phage display technology. Then, silver nanoparticles (AgNP) were assembled electrostatically on its surface capsid protein (M13@Ag) to achieve specific clearance of Fn and remodel the tumor-immune microenvironment. Both in vitro and in vivo studies showed that of M13@Ag treatment could scavenge Fn in gut and lead to reduction in MDSC amplification in the tumor site. In addition, antigen-presenting cells (APCs) were activated by M13 phages to further awaken the host immune system for CRC suppression. M13@Ag combined with immune checkpoint inhibitors (α-PD1) or chemotherapeutics (FOLFIRI) significantly prolonged overall mouse survival in the orthotopic CRC model.

scholarly journals Macrophages, as a Promising Strategy to Targeted Treatment for Colorectal Cancer Metastasis in Tumor Immune Microenvironment

2021 ◽  
Vol 12 ◽  
Author(s):  
Yingru Zhang ◽  
Yiyang Zhao ◽  
Qi Li ◽  
Yan Wang
Keyword(s):  
Colorectal Cancer ◽  
Cancer Metastasis ◽  
Metastatic Potential ◽  
Vital Role ◽  
Phenotypic Switching ◽  
High Plasticity ◽  
Immune Microenvironment ◽  
Promising Strategy ◽  
Tumor Immune Microenvironment ◽  
Colorectal Cancer Metastasis

The tumor immune microenvironment plays a vital role in the metastasis of colorectal cancer. As one of the most important immune cells, macrophages act as phagocytes, patrol the surroundings of tissues, and remove invading pathogens and cell debris to maintain tissue homeostasis. Significantly, macrophages have a characteristic of high plasticity and can be classified into different subtypes according to the different functions, which can undergo reciprocal phenotypic switching induced by different types of molecules and signaling pathways. Macrophages regulate the development and metastatic potential of colorectal cancer by changing the tumor immune microenvironment. In tumor tissues, the tumor-associated macrophages usually play a tumor-promoting role in the tumor immune microenvironment, and they are also associated with poor prognosis. This paper reviews the mechanisms and stimulating factors of macrophages in the process of colorectal cancer metastasis and intends to indicate that targeting macrophages may be a promising strategy in colorectal cancer treatment.

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