scholarly journals MS4A1 expression and function in T cells in the colorectal cancer tumor microenvironment

2021 ◽  
Vol 360 ◽  
pp. 104260
Author(s):  
T. William Mudd ◽  
Chunwan Lu ◽  
John D. Klement ◽  
Kebin Liu
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Cancer Tumor ◽  
And Function

scholarly journals FABP4 Might be an Indicator of the Status of Tumor Microenvironment in Colorectal Cancer

2021 ◽  
Author(s):  
Lijun Ning ◽  
Yuqing Yan ◽  
Tianying Tong ◽  
Ziyun Gao ◽  
Zhe Cui ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Cox Regression ◽  
Nk Cell ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Fatty Acid Binding ◽  
Cox Regression Analysis ◽  
The Status

Abstract Background: As tumor microenvironment (TME) play an indispensable role in tumorigenesis of colorectal cancer, this study performs a bunch of bioinformatics analysis to identify the indicator of the status of TME in Colorectal cancer (CRC). Results: In the presented study, we applied CIBERSORT and ESTIMATE computational methods to calculate the proportion of tumor-infiltrating immune cells (TICs) and the amount of immune and stromal components in 444 COAD-READ cases from The Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) were analyzed by COX regression analysis and protein–protein interaction (PPI) network construction. Then, fatty acid-binding protein four ( FABP4 ) was determined as a predictive factor by the intersection analysis of univariate COX and PPI. Further analysis revealed that FABP4 expression was positively correlated with the clinical pathologic characteristics (clinical stage, distant metastasis) and negatively correlated with the survival of CRC patients. Gene Set Enrichment Analysis (GSEA) showed that the genes in the high-expression FABP4 group were mainly enriched in immune-related activities. In the low-expression FABP4 group, the genes were enriched in metabolic pathways. CIBERSORT analysis for the proportion of TICs revealed that NK cell, CD4 + T cells and CD8 + T cells were negatively correlated with FABP4 expression, suggesting that FABP4 might be a potential prognostic factor of CRC patients. Conclusion: Our study has developed a new biomarker (FABP4) that can predict the status of tumor microenvironment in Colorectal cancer. Keywords: FABP4, tumor microenvironment, ESTIMATE, CIBERSORT, colorectal cancer

Network analysis to reveal BTK as a link between myeloid and T cells in TLR signaling in colorectal cancer.

2020 ◽  
Vol 38 (5_suppl) ◽  
pp. 30-30
Author(s):  
Justin Hummel ◽  
Yuanyuan Shen ◽  
Iiulia Innokenteva ◽  
Christos Papageorgiou ◽  
Chi-Ren Shyu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
Network Analysis ◽  
Tumor Microenvironment ◽  
Myeloid Cells ◽  
Cell Types ◽  
The Cancer Genome Atlas ◽  
P Value ◽  
Tlr Signaling ◽  
Critical Link

30 Background: Colorectal cancer (CRC) is the second-leading cause of cancer mortality in the US today. Recent advances in immunotherapy have only been shown to benefit a limited subgroup of patients with CRC. In other malignancies, activation of Toll-like receptors (TLRs) has been shown to overcome resistance to immunotherapy, such as immune checkpoint inhibition (ICI). In this study, using publicly available data and informatics-based analysis, we identified BTK as a critical link between TLR signaling and T cells in the CRC tumor microenvironment. Methods: Using RNA-seq data from The Cancer Genome Atlas (TCGA) and the Microenvironment Cell Populations (MCP)-Counter, abundance scores were generated for the tumor microenvironment of each patient. A curated TLR gene panel was generated using Reactome and GO. Pearson analysis was used to evaluate each pairwise combination of genes and cell-types. Significance was determined by the correlation coefficient, r ≥ | 0.7 | with a p-value < 0.05. Network analysis was performed using the Girvan–Newman algorithm to establish critical connections across these features. Results: After establishing a 453 gene TLR panel and creating MCP-Counter scores, correlation analysis demonstrated strong correlations between 54 different genes and 7 cell-types. As expected the most genes were associated with monocytic lineage cells' (30) and 'myeloid dendritic cells' (7). Only 5 genes were significantly associated with 'T cells'. Genes and cell-types that were highly correlated were then further analyzed for network association. From this analysis, BTK was identified as a critical edge acting as the primary link between ‘myeloid cells’ and ‘T cells’. Conclusions: Developing novel strategies for the treatment of CRC is critical and immunotherapy represents an area ripe for advancement. Informatics based analysis combined with publicly available data provides us with an opportunity to shape pre-clinical and translational studies. Using this approach, we have identified BTK as a critical link between myeloid cells and T cells in the tumor microenvironment in CRC. Further studies in our laboratory will focus confirming these findings for translation into patients.

The correlation between tumor microenvironment and the clonality of the T-cell repertoire in lung cancer and colorectal cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14524-e14524
Author(s):  
Hua Cao ◽  
Jingxian Duan ◽  
Shunda Jiang ◽  
Tianhao Mu ◽  
Ruilian Xu
Keyword(s):  
Colorectal Cancer ◽  
Lung Cancer ◽  
T Cells ◽  
T Cell ◽  
Tumor Microenvironment ◽  
Clonal Expansion ◽  
T Helper ◽  
T Cell Clonality ◽  
Cell Clonality ◽  
Cell Clonal Expansion

e14524 Background: The tumor microenvironment has been shown to affect the responsiveness of immunotherapy. Effective anti-tumor immune response requires the activation and expansion of specific antigen-reactive T cell clones. It was reported that increased T cell clonality was associated with improved response to immunotherapy. However, what type of tumor microenvironment facilitates T cell clonal expansion remained controversial. The study aims to investigate the correlation between tumor microenvironment and the clonality of the T cell repertoire in lung cancer and colorectal cancer. Methods: 4 lung cancer patients and 4 colorectal cancer patients were enrolled in this study. Tumor tissues and peripheral blood samples were collected for RNA sequencing and T cell receptor CDR3 sequencing. The infiltration levels of 28 immune cells were estimated based on the mRNA expression of the genetic markers. The T cell clonality was defined as 1-Peilou’s evenness. Data were presented as mean± S.E.M. Results: The mean T cell clone counts in the blood samples of the 8 patients were 25676±4782 (ranging from 10259 to 45016), and the mean clonality of the TCR repertoires was 0.20±0.02 (ranging from 0.11 to 0.27). The clonality of T cells in colorectal cancer patients was similar to that of the lung cancer patients (0.22±0.02 versus 0.18±0.03, p = 0.31), showing comparable potentials of antigenic responses. The tumor infiltration of regulatory T cells, type 17 T helper cells, CD56bright natural killer cells, and natural killer cells varied greatly among patients, the coefficient of variation of those cells were 54.61%, 54.61%, 54.43%, and 55.62% respectively. In contrast, the coefficient of variation of monocytes was 23.34%, displaying a relatively even distribution among patients. The Pearson’s correlation coefficient was calculated to show the correlation between T cell clonality and the infiltration level of all 28 types of immune cells. Notably, only the infiltration of type 17 T helper cells significantly associated with T cell clonality, the positive correlation gave an R square value of 0.68 (r = 0.82, 95% confidence interval of 0.04-0.98, p = 0.04). The infiltration levels of CD4+ T cells, CD8+ T cells, regulatory T cells, type 1 and type 2 T cells, and gamma delta T cells were not affected by T cell clonal expansion. The expression of B cells, dendritic cells, macrophages, natural killer cells, and monocytes did not correlate with T cell clonal expansion. However, the abundance of neutrophils appears to positively correlate with T cell clonality (p = 0.09). Conclusions: The clonal expansion was significantly associated with the infiltration of type 17 T helper cells but not other subtypes of T cells, showing that the type 17 T helper cells are crucial to the antigenic responses in lung cancer and colorectal cancer. A neutrophil enriched tumor microenvironment may facilitate T cell clonal expansion.

scholarly journals STUDY OF TUMOR MICROENVIRONMENT AND HOST RESPONSE IN COLORECTAL CANCER: IMMUNOHISTOCHEMICAL AND CLINICOPATHOLOGICAL APPROACH

2019 ◽  
pp. 32-37
Author(s):  
NORIA OTHMAN RAFFALLA ◽  
SUZAN MOHAMED FAROUK HELAL ◽  
AMANY ABD EL-BARY ABD EL-LATIF ◽  
RASHA OMAR ELSAKA
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Regulatory T Cells ◽  
Cytotoxic T Cells ◽  
Tumor Infiltrating Lymphocytes ◽  
Tumor Associated Macrophages ◽  
Tissue Samples ◽  
Level Of Significance

Objective: This study aimed to evaluate the immunohistochemical expression of forkhead boxP3 (Foxp3), CD8, CD68, and CD21 in stroma between tumor cells of colorectal cancer (CRC) patients and examines the relationship between these variables and clinicopathological parameter and patients’ prognosis. Methods: In this work, 50 cases of colorectal carcinomas were included and immunohistochemical evaluation of Foxp3, CD8, CD68, and CD21 in tumor tissue samples. Results: Tumor-infiltrating lymphocytes (TILs) including cytotoxic T cells and regulatory T cells as well as tumor-associated macrophages and follicular dendritic cells (FDCs) were studied in the stroma of the tumor using immunostaining technique for CD8, Foxp3, CD68, and CD21, respectively. Cases were followed up. CD8-positive cytotoxic T cells, Foxp3-positive regulatory T cells, and CD21 positive-FDCs were significantly more pronounced in early tumors and those with longer overall survival. On the other hand, CD68 positive macrophages were more encountered in late stage and metastatic tumors as well as tumors with shorter overall survival, but these results not reached the level of significance. Conclusion: We concluded that (TILs) and FDCs are conferring better prognosis in CRCs, they may act synergistically in stimulating a protective immune response in the tumor microenvironment that hinders tumor progression, while the role of tumor-associated macrophages in CRCs is still controversial and needs further studies.

scholarly journals Systemic Interleukins’ Profile in Early and Advanced Colorectal Cancer

2021 ◽  
Vol 23 (1) ◽  
pp. 124
Author(s):  
Paulina Czajka-Francuz ◽  
Sylwia Cisoń-Jurek ◽  
Aleksander Czajka ◽  
Maciej Kozaczka ◽  
Jerzy Wojnar ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Regulatory T Cells ◽  
Immune Cells ◽  
Advanced Colorectal Cancer ◽  
Experimental Studies ◽  
The Body ◽  
Lymphoid Cells ◽  
T Helper

Tumor microenvironment (TME) is characterized by mutual interactions of the tumor, stromal and immune cells. Early and advanced colorectal tumors differ in structure and present altered serum cytokine levels. Mutual crosstalk among TME infiltrating cells may shift the balance into immune suppressive or pro-inflammatory, antitumor response this way influencing patients’ prognosis. Cancer-related inflammation affects all the body and this way, the systemic level of cytokines could reflect TME processes. Despite numerous studies, it is still not known how systemic cytokines levels change during colorectal cancer (CRC) tumor development. Better understanding tumor microenvironment processes could help in planning therapeutic interventions and more accurate patient prognosis. To contribute to the comprehension of these processes within TME, we reviewed cytokines levels from clinical trials in early and advanced colorectal cancer. Presented data were analyzed in the context of experimental studies and studies analyzing tumor infiltration with immune cells. The review summarizes clinical data of cytokines secreted by tumor microenvironment cells: lymphocytes T helper 1 (Th1), lymphocytes T helper 2 (Th2), lymphocytes T helper 17 (Th17), regulatory T cells (Treg cells), regulatory T cells (Breg cells), M1/M2 macrophages, N1/N2 neutrophils, myeloid-derived suppressor cells (MDSC), dendritic cells (DC), innate lymphoid cells (ILC) natural killer (NK) cells and tumor cells.

scholarly journals Immunosuppressive Roles of Galectin-1 in the Tumor Microenvironment

Biomolecules ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1398
Author(s):  
Yanyu Huang ◽  
Hsiao-Chi Wang ◽  
Junwei Zhao ◽  
Ming-Heng Wu ◽  
Tsung-Chieh Shih
Keyword(s):  
Tumor Microenvironment ◽  
Cell Function ◽  
Immune Cell ◽  
Immune Escape ◽  
Immune Surveillance ◽  
Human Tumor ◽  
Immune Cell Function ◽  
Tumor Immune Escape ◽  
Cancer Tumor ◽  
And Function

Evasion of immune surveillance is an accepted hallmark of tumor progression. The production of immune suppressive mediators by tumor cells is one of the major mechanisms of tumor immune escape. Galectin-1 (Gal-1), a pivotal immunosuppressive molecule, is expressed by many types of cancer. Tumor-secreted Gal-1 can bind to glycosylated receptors on immune cells and trigger the suppression of immune cell function in the tumor microenvironment, contributing to the immune evasion of tumors. The aim of this review is to summarize the current literature on the expression and function of Gal-1 in the human tumor microenvironment, as well as therapeutics targeting Gal-1.

scholarly journals GARP: A Key Target to Evaluate Tumor Immunosuppressive Microenvironment

Biology ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 836
Author(s):  
Alexanne Bouchard ◽  
Bertrand Collin ◽  
Carmen Garrido ◽  
Pierre-Simon Bellaye ◽  
Evelyne Kohli
Keyword(s):  
T Cells ◽  
Molecular Imaging ◽  
Growth Factor ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Immune Evasion ◽  
Transforming Growth Factor ◽  
Immunosuppressive Microenvironment ◽  
And Function

Glycoprotein-A repetitions predominant (GARP) is the docking receptor for latent transforming growth factor (LTGF-β) and promotes its activation. In cancer, increased GARP expression has been found in many types of cancer. GARP is expressed by regulatory T cells and platelets in the tumor microenvironment (TME) and can be also expressed by tumor cells themselves. Thus, GARP can be widely present in tumors in which it plays a major role in the production of active TGF-β, contributing to immune evasion and cancer progression via the GARP-TGF-β pathway. The objective of this review is to highlight GARP expression and function in cancer and to evaluate the potential of membrane GARP as a predictive and therapeutic follow-up biomarker that could be assessed, in real time, by molecular imaging. Moreover, as GARP can be secreted, a focus will also be made on soluble GARP as a circulating biomarker.

scholarly journals Extracellular Vesicles Derived From Colorectal Cancer Affects CD8 T Cells: An Analysis Based on Body Mass Index

2020 ◽  
Vol 8 ◽  
Author(s):  
Nadiah Abu ◽  
Norahayu Othman ◽  
Nur’ Syahada Ab Razak ◽  
Nurul Ainaa’ Adilah Rus Bakarurraini ◽  
Siti Nurmi Nasir ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Body Mass Index ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Body Mass ◽  
Extracellular Vesicles ◽  
Cd8 T Cells ◽  
Survival Rates ◽  
The Body ◽  
Low Bmi

Colorectal cancer (CRC) is one of the most widely diagnosed cancers worldwide. It has been shown that the body-mass index (BMI) of the patients could influence the tumor microenvironment, treatment response, and overall survival rates. Nevertheless, the mechanism on how BMI affects the tumorigenesis process, particularly the tumor microenvironment is still elusive. Herein, we postulate that extracellular vesicles (EVs) from CRC patients and non-CRC volunteers with different BMI could affect immune cells differently, in CD8 T cells particularly. We isolated the EVs from the archived serum of CRC patients with high and low BMI, as well as healthy controls with similar BMI status. The EVs were further characterized via electron microscopy, western blot and dynamic light scattering. Then, functional analysis was performed on CD8 T cells including apoptosis, cell proliferation, gene expression profiling and cytokine release upon co-incubation with the different EVs. Our results suggest that CRC-derived EVs were able to regulate the CD8 T cells. In some assays, low BMI EVs were functionally different than high BMI EVs. This study highlights the possible difference in the regulatory mechanism of cancer patients-derived EVs, especially on CD8 T cells.

Sign in / Sign up

Export Citation Format

Share Document