Colon-specific immune microenvironment regulates cancer progression versus rejection

Trimaglio, Giulia; Tilkin–Mariamé, Anne-Françoise; Féliu, Virginie; Lauzéral-Vizcaino, Françoise; Tosolini, Marie; Valle, Carine; Ayyoub, Maha; Vergnolle, Nathalie; Rombouts, Yoann; Devaud, Christel

doi:10.1080/2162402x.2020.1790125

Cited by 22 publications

(28 citation statements)

References 55 publications

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“…The pathogenesis of CC is not fully clear, and the optimal diagnosis and management of CC is still a source of debate ( Arredondo et al, 2020 ; Biller and Schrag, 2021 ). In recent years, immunotherapy has emerged as a novel therapeutic option for CC, with promising outcomes ( Mlecnik et al, 2020 ; Trimaglio et al, 2020 ). However, there are great differences in the curative effect among patients, and many problems need to be solved.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Analysis of Necroptosis-Related Long Noncoding RNA Immune Infiltration and Prediction of Prognosis in Patients With Colon Cancer

Liu

Huang

Chen

et al. 2022

Front. Mol. Biosci.

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Colon cancer (CC) is one of the most frequent malignancies in the world, with a high rate of morbidity and death. In CC, necroptosis and long noncoding RNA (lncRNAs) are crucial, but the mechanism is not completely clear. The goal of this study was to create a new signature that might predict patient survival and tumor immunity in patients with CC. Expression profiles of necroptosis-related lncRNAs in 473 patients with CC were retrieved from the TCGA database. A consensus clustering analysis based on differentially expressed (DE) genes and a prognostic model based on least absolute shrinkage and selection operator (LASSO) regression analysis were conducted. Clinicopathological correlation analysis, expression difference analysis, PCA, TMB, GO analysis, KEGG enrichment analysis, survival analysis, immune correlation analysis, prediction of clinical therapeutic compounds, and qRT–PCR were also conducted. Fifty-six necroptosis-related lncRNAs were found to be linked to the prognosis, and consensus clustering analysis was performed. There were substantial variations in survival, immune checkpoint expression, clinicopathological correlations, and tumor immunity among the different subgroups. Six lncRNAs were discovered, and patients were split into high-risk and low-risk groups based on a risk score generated using these six lncRNAs. The survival time of low-risk patients was considerably longer than that of high-risk patients, indicating that these lncRNAs are directly associated with survival. The risk score was associated with the tumor stage, infiltration depth, lymph node metastasis, and distant metastasis. After univariate and multivariate Cox regression analysis, the risk score and tumor stage remained significant. Cancer- and metabolism-related pathways were enriched by KEGG analyses. Immune infiltration was shown to differ significantly between high- and low-risk patients in a tumor immunoassay. Eight compounds were screened out, and qRT–PCR confirmed the differential expression of the six lncRNAs. Overall, in CC, necroptosis-related lncRNAs have an important function, and the prognosis of patients with CC can be predicted by these six necroptosis-related lncRNAs. They may be useful in the future for customized cancer therapy.

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Section: Introductionmentioning

confidence: 99%

Comprehensive Analysis of Necroptosis-Related Long Noncoding RNA Immune Infiltration and Prediction of Prognosis in Patients With Colon Cancer

Liu

Huang

Chen

et al. 2022

Front. Mol. Biosci.

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“…40 The inflammatory tumor microenvironment eventually leads to tumor progression and metastasis. [41][42][43] To investigate the role of tumor milieu with FUT7, we analyzed the relationship between FUT7 expression and immune cell infiltration. Growing evidence demonstrated that the infiltration and activation of immune cells were believed to be closely associated with tumor processes, such as breast cancer, 44 lung cancer, 45 uterine corpus endometrial carcinoma, 46 and bladder cancer.…”

Section: Discussionmentioning

confidence: 99%

FUT7 Promotes the Epithelial–Mesenchymal Transition and Immune Infiltration in Bladder Urothelial Carcinoma

Liu¹,

Zheng²,

Chen³

et al. 2021

JIR

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Background Bladder urothelial carcinoma (BLCA) is one of the most frequently appearing, lethal and aggressive malignancies of the genitourinary system with growing morbidity and mortality, which affects human health seriously. Protein glycosylation, catalyzed by specific glycosyltransferase, has been found to be abnormal in several diseases, especially cancer. Fucosyltransferase VII (FUT7), one of the fucosyltransferases, was observed abnormally expressed in various cancers, however, the role of FUT7 in BLCA, and the association between its expression and clinical outcomes or immune infiltration remains unclear. Methodology FUT7 expression in BLCA was analyzed in Oncomine database, which was further confirmed with immunohistochemistry and ELISA. The prognostic value of FUT7 for BLCA was evaluated with PrognoScan database, and its genetic alteration was examined in cBioPortal database. The proliferation, migration, invasion and epithelial–mesenchymal transition (EMT) changes of bladder cancer cells after FUT7 siRNA or cDNA transfection were determined by CCK8, colony formation, transwell and Western blot, respectively. The correlation between FUT7 expression and immune infiltration levels was analyzed in TIMER and TISIDB databases, and the methylation level of FUT7 was detected in UALCAN database. Results The results showed that the expression of FUT7 was increased in BLCA, and patients with high FUT7 level were predicted to have lower overall survival and disease-specific survival rates, which were not influenced by FUT7 genetic alterations. Downregulation FUT7 inhibited the proliferation, migration, invasion and EMT of bladder cancer cells, whereas upregulation of FUT7 showed the opposite effects. We found that FUT7 was positively correlated with immune cell infiltration levels (CD8+ T cells, CD4+T cells, macrophage, neutrophil and dendritic cells), and also the expression of gene markers of immune cells. The negative correlation between FUT7 expression and FUT7 methylation level was observed, among which FUT7 expression was positively correlated with the abundance of 28 kinds of tumor-infiltrating lymphocytes (TILs), while FUT7 methylation level was negatively correlated with TILs. Conclusion Altogether, these findings suggested that FUT7 possessed the potential to serve as a detection biomarker or immunotherapeutic target for BLCA.

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“…The importance and decisive role of the immune microenvironment in determining tumor fate has been elegantly described in a recent study by Devaud et al, where the authors identified two opposing immune response profiles with either pro- or anti-tumor properties that establish at early stage of tumor development and determine tumor progression vs. rejection [ 97 ]. Phenotypic differences in T cell infiltration within the TME can be summarized into three categories: the “immune-inflamed/hot” phenotype, in which CD8 + T cells infiltrate the tumor; the “immune-excluded” phenotype, in which infiltrating CD8 + T cells accumulate in the tumor stroma and the “immune-desert/cold” phenotype, in which CD8 + T cells are low or absent from the tumor and the stroma [ 98 , 99 ].…”

Section: The Prognostic Value Of the Tumor Microenvironmentmentioning

confidence: 99%

Emerging Trends for Radio-Immunotherapy in Rectal Cancer

Corrò

Dutoit

Koessler

2021

Cancers

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Rectal cancer is a heterogeneous disease at the genetic and molecular levels, both aspects having major repercussions on the tumor immune contexture. Whilst microsatellite status and tumor mutational load have been associated with response to immunotherapy, presence of tumor-infiltrating lymphocytes is one of the most powerful prognostic and predictive biomarkers. Yet, the majority of rectal cancers are characterized by microsatellite stability, low tumor mutational burden and poor T cell infiltration. Consequently, these tumors do not respond to immunotherapy and treatment largely relies on radiotherapy alone or in combination with chemotherapy followed by radical surgery. Importantly, pre-clinical and clinical studies suggest that radiotherapy can induce a complete reprograming of the tumor microenvironment, potentially sensitizing it for immune checkpoint inhibition. Nonetheless, growing evidence suggest that this synergistic effect strongly depends on radiotherapy dosing, fractionation and timing. Despite ongoing work, information about the radiotherapy regimen required to yield optimal clinical outcome when combined to checkpoint blockade remains largely unavailable. In this review, we describe the molecular and immune heterogeneity of rectal cancer and outline its prognostic value. In addition, we discuss the effect of radiotherapy on the tumor microenvironment, focusing on the mechanisms and benefits of its combination with immune checkpoint inhibitors.

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Colon-specific immune microenvironment regulates cancer progression versus rejection

Cited by 22 publications

References 55 publications

Comprehensive Analysis of Necroptosis-Related Long Noncoding RNA Immune Infiltration and Prediction of Prognosis in Patients With Colon Cancer

Comprehensive Analysis of Necroptosis-Related Long Noncoding RNA Immune Infiltration and Prediction of Prognosis in Patients With Colon Cancer

FUT7 Promotes the Epithelial–Mesenchymal Transition and Immune Infiltration in Bladder Urothelial Carcinoma

Emerging Trends for Radio-Immunotherapy in Rectal Cancer

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