Immune Regulatory Processes of the Tumor Microenvironment under Malignant Conditions

Pansy, Katrin; Uhl, Barbara; Krstić, Jelena; Szmyra, Marta; Fechter, Karoline; Santiso, Ana; Thüminger, Lea; Greinix, Hildegard; Kargl, Julia; Prochazka, Katharina; Feichtinger, Julia; Deutsch, Alexander

doi:10.3390/ijms222413311

Cited by 66 publications

(51 citation statements)

References 461 publications

(464 reference statements)

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“…To further grasp the extent of immune infiltration between the two groups, we used ESTIMATE, CIBERSORT, and ssGSEA, which suggested that the tumor immune response in group 1 may be more active than group 2. TME consists of more than 30 different tumor-infiltrating non-malignant cell types, as well as ECM, which both promote tumorigenesis and play key roles in anti-tumor immune responses [ 43 ]. Tumor-associated macrophages (TAMs) are the main component of TME, and have a vital function in the proliferation, invasion and metastasis of tumor cells and the inhibition of T cells anti-tumor immune response.…”

Section: Discussionmentioning

confidence: 99%

RGS1 and related genes as potential targets for immunotherapy in cervical cancer: computational biology and experimental validation

et al. 2022

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Background Effective treatment is needed for advanced, inoperable, or chemotherapy-resistant cervical cancer patients. Immunotherapy has become a new treatment modality for cervical cancer patients, and there is an urgent need to identify additional targets for cervical cancer immunotherapy. Methods In this study the core gene, RGS1, which affects immune status and the FIGO stage of cervical cancer patients was identified by WGCNA analysis and differential analysis using TCGA database. 10 related genes interacting with RGS1 were identified using PPI network, and the functional and immune correlations were analyzed. Based on the expression of RGS1 and related genes, the consensus clustering method was used to divide CESC patients into two groups (group 1, high expression of RGS1; group 2, low expression of RGS1). Then, the functional enrichment analysis was used to search for the functional differences in differentially expressed genes (DEGs) between group 1 and group 2. Immune infiltration analysis was performed using ESTIMATE, CIBERSORT, and ssGSEA, and the differences in expression of immune checkpoint inhibitors (ICIs) targets were assessed between the two groups. We investigated the effect of RGS1 on the clinical relevance of CESC patients, and experimentally verified the differences in RGS1 expression between cervical cancer patient tissues and normal cervical tissues, the role of RGS1 in cell function, and the effect on tumor growth in tumor-bearing mice. Results We found that RGS1 was associated with CD4, GNAI3, RGS2, GNAO1, GNAI2, RGS20, GNAZ, GNAI1, HLA-DRA and HLA-DRB1, especially CD4 and RGS2. Functional enrichment of DEGs was associated with T cell activation. Compared with group 2, group 1 had stronger immune infiltration and higher ICI target expression. RGS1 had higher expression in cervical cancer tissues than normal tissues, especially in HPV-E6 positive cancer tissues. In cervical cancer cell lines, knockdown of RGS1 can inhibited cell proliferation, migration, invasion, and tumor growth in nude mice and promoted apoptosis. Conclusions RGS1, as an oncogenic gene of cervical cancer, affects the immune microenvironment of patients with cervical cancer and may be a target of immunotherapy.

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Section: Discussionmentioning

confidence: 99%

RGS1 and related genes as potential targets for immunotherapy in cervical cancer: computational biology and experimental validation

et al. 2022

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“…The tumor microenvironment (TME) is the cellular environment influencing the process of tumors and is composed of immune cells (both innate and acquired immune cells), nonimmune stromal cells (such as fibroblasts, endothelial cells, and various tissue-associated cells), and extracellular matrix proteins ( Monteran and Erez, 2019 ; Wculek et al, 2020 ; Pansy et al, 2021 ). Among them, all kinds of cells interact with each other and cancer cells through the secretion of various cytokines, chemokines, and other signals, so they play a key role in the regulation of the tumor immune response.…”

Section: Discussionmentioning

confidence: 99%

Integrated Analysis Reveals Critical Ferroptosis Regulators and FTL Contribute to Cancer Progression in Hepatocellular Carcinoma

Wang

et al. 2022

Front. Genet.

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Background: The carcinogenesis and prognosis of hepatocellular carcinoma (HCC) involve complex molecular mechanisms, and ferroptosis is related to the development and therapeutic efficacy of HCC, but the specific mechanism and prognostic role of ferroptosis-related genes in HCC have not been elucidated.Methods: Differentially expressed gene analysis, Cox regression, and unsupervised consensus clustering were applied to identify crucial ferroptosis regulators and establish ferroptosis-related subtypes in HCC. Random forest analysis and survival analysis were adopted to confirm FTL as the hub prognostic and diagnostic ferroptosis regulator in HCC.Results: The ferroptosis-related subtypes based on the crucial prognostic ferroptosis regulators showed that patients in fescluster A had a higher survival probability (p < 0.001) and better clinical characteristics than patients in fescluster B in the TCGA-LIHC cohort. Patients with a high tumor mutation burden (TMB) in fescluster B presented a significantly poorer prognosis. FTL was the core ferroptosis regulator, and its low expression revealed a significant survival advantage compared with its high expression (p = 0.03). The expression and predictive value of FTL were both closely related to the clinical features (p < 0.05). Expression of FTL accurately distinguished HCC from normal tissues in the TCGA-LIHC cohort, ICGC cohort, and GSE14520 dataset. In addition, higher infiltrating fractions of immune cells, such as activated CD8+ T cells and Gamma delta T cells, mainly enriched immune-related signaling pathways, including the IL2-STAT3 signaling pathway and interferon-gamma response signaling pathway, and higher expression of immune checkpoints, including PDCD1, CTLA4, TIGIT, and CD83, were presented in patients with high FTL expression (p < 0.05). Patients with high FTL were more sensitive to some targeted drugs, such as cisplatin, dasatinib, and sorafenib, than those with low FTL (p < 0.05). A nomogram based on FTL accurately predicted the prognosis of HCC. Further knockdown of FTL was determined to significantly inhibit cell proliferation and migration in HCC.Conclusion: Our study validated ferroptosis-related subtypes and FTL with effective prognostic value in HCC and was beneficial for identifying candidates suitable for targeted drug therapy and immunotherapy, thereby offering further insight into individual treatment strategies to improve disease outcomes in HCC patients.

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“…The tumor microenvironment (TME) is the local ecological environment on which tumor cells depend, and it includes immune cells, endothelial cells, microvasculature, and cytokines [ 20 ]. The interaction between the tumor and the immune cells undergoes a remodelling of the immune system, and eventually, tumor cells use a series of mechanisms to undergo immune escape or tumor dormancy.…”

Section: Introductionmentioning

confidence: 99%

The Value of m5C-Related lncRNAs in the Prognostic Assessment and Immunotherapy of Stomach Adenocarcinoma

Zhu

Kong

et al. 2022

BioMed Research International

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Long noncoding RNAs (lncRNAs) are closely associated with a variety of tumors, including stomach adenocarcinoma (STAD). However, the role of 5-methylcytosine- (m5C-) related lncRNAs in STAD is still uncertain. This study investigated the value of m5C-related lncRNAs in prognostic evaluation and immunotherapy of STAD. STAD transcriptome sequencing data were downloaded from The Cancer Genome Atlas (TCGA) database, and m5C-related lncRNAs were screened by Pearson correlation analysis. A prognostic m5C-related lncRNA signature (m5CRLSig) associated with STAD was established using univariate and multivariate Cox regression analysis. We constructed a prognostic risk model for STAD with six m5C-related lncRNAs. The receiver operating characteristic (ROC) curve was used to examine the predictive efficacy. Univariate and multifactorial Cox regression analysis and principal component analysis (PCA) validated m5CRLSig as an independent factor of STAD prognosis. The clinicopathological characteristics of the model showed higher risk scores for stages II-IV, grade 3, N1-3, and death status. The calibration curve of a nomogram revealed that the nomogram had an excellent predictive function for survival risk. Furthermore, the expression of six m5C-related lncRNAs in STAD and paracancerous tissues was detected by quantitative real-time PCR (qRT-PCR), which verified the feasibility of the m5CRLSig as a prognostic marker for STAD. m5C-related lncRNAs were linked to multiple immune-associated pathways, according to gene set enrichment analysis (GSEA). CIBERSORT analysis indicated that m5CRLSig was involved in immune cell infiltration. Risk score was associated with immune checkpoint gene expression, immune function scores, and chemotherapeutic drug sensitivity. Therefore, m5CRLSig can efficiently assess the prognosis of STAD patients and can be used as a biological marker for immunotherapy.

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Immune Regulatory Processes of the Tumor Microenvironment under Malignant Conditions

Cited by 66 publications

References 461 publications

RGS1 and related genes as potential targets for immunotherapy in cervical cancer: computational biology and experimental validation

RGS1 and related genes as potential targets for immunotherapy in cervical cancer: computational biology and experimental validation

Integrated Analysis Reveals Critical Ferroptosis Regulators and FTL Contribute to Cancer Progression in Hepatocellular Carcinoma

The Value of m5C-Related lncRNAs in the Prognostic Assessment and Immunotherapy of Stomach Adenocarcinoma

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