RNA Modification of N6-Methyladenosine Predicts Immune Phenotypes and Therapeutic Opportunities in Kidney Renal Clear Cell Carcinoma

Li, Huihuang; Hu, Jiao; Yu, Anze; Othmane, Belaydi; Guo, Tao; Liu, Jinhui; Cheng, Chunliang; Chen, Jinbo; Zu, Xiongbing

doi:10.3389/fonc.2021.642159

Cited by 30 publications

(31 citation statements)

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“…Moreover, it has been found that m 6 A modification influence the infiltration, activation and function of immune cell in TME, which makes m 6 A-targeting a promising therapy (65,69). In renal clear-cell carcinoma (RCC), low m 6 A score group was characterized by a hot/inflammatory TME, which may be more sensitive to anti-tumor immunotherapy (70). Similar result was found in a RCC cohort that m 6 A score was negatively correlated with antigen processing machinery (APM) (71).…”

Section: Role Of M 6 a In Tme Immune Responsementioning

confidence: 99%

“…In renal clear-cell carcinoma (RCC), low m 6 A score group was characterized by a hot/inflammatory TME, which may be more sensitive to anti-tumor immunotherapy ( 70 ). Similar result was found in a RCC cohort that m 6 A score was negatively correlated with antigen processing machinery (APM) ( 71 ).…”

Section: Role Of M 6 a In Anti-tumor Immune Responsementioning

confidence: 99%

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N6-Methyladenosine in Cancer Immunotherapy: An Undervalued Therapeutic Target

Quan

Othmane

et al. 2021

Front. Immunol.

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N6-methylation of adenosine (m6A), a post-transcriptional regulatory mechanism, is the most abundant nucleotide modification in almost all types of RNAs. The biological function of m6A in regulating the expression of oncogenes or tumor suppressor genes has been widely investigated in various cancers. However, recent studies have addressed a new role of m6A modification in the anti-tumor immune response. By modulating the fate of targeted RNA, m6A affects tumor-associated immune cell activation and infiltration in the tumor microenvironment (TME). In addition, m6A-targeting is found to affect the efficacy of classical immunotherapy, which makes m6A a potential target for immunotherapy. Although m6A modification together with its regulators may play the exact opposite role in different tumor types, targeting m6A regulators has been shown to have wide implications in several cancers. In this review, we discussed the link between m6A modification and tumor with an emphasis on the importance of m6A in anti-tumor immune response and immunotherapy.

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Section: Role Of M 6 a In Tme Immune Responsementioning

confidence: 99%

Section: Role Of M 6 a In Anti-tumor Immune Responsementioning

confidence: 99%

N6-Methyladenosine in Cancer Immunotherapy: An Undervalued Therapeutic Target

Quan

Othmane

et al. 2021

Front. Immunol.

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“…ccRCC is not sensitive to radiotherapy and chemotherapy [ 5 ]; therefore, more effective targeted therapy is needed. Other studies have explored the possible molecular markers or therapeutic targets of ccRCC from different perspectives, such as autophagy associated long noncoding RNAs (lncRNAs) [ 6 ], methylation modification of m6A [ 7 ], DNA methylation [ 8 ], and immune invasion [ 9 ]. We set out to find new potential targets from a metabolic perspective.…”

Section: Introductionmentioning

confidence: 99%

Identification of Prognostic Metabolism-Related Genes in Clear Cell Renal Cell Carcinoma

Chen

Liang

Chen

et al. 2021

Journal of Oncology

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Background. Clear cell renal cell carcinoma (ccRCC) is a cancer with abnormal metabolism. The purpose of this study was to investigate the effect of metabolism-related genes on the prognosis of ccRCC patients. Methods. The data of ccRCC patients were downloaded from the TCGA and the GEO databases and clustered using the nonnegative matrix factorization method. The limma software package was used to analyze differences in gene expression. A random forest model was used to screen for important genes. A novel Riskscore model was established using multivariate regression. The model was evaluated based on the metabolic pathway, immune infiltration, immune checkpoint, and clinical characteristics. Results. According to metabolism-related genes, kidney clear cell carcinoma (KIRC) datasets downloaded from TCGA were clustered into two groups and showed significant differences in prognosis and immune infiltration. There were 667 differentially expressed genes between the two clusters, of which 408 were screened by univariate analysis. Finally, 12 differentially expressed genes (MDK, SLC1A1, SGCB, C4orf3, MALAT1, PILRB, IGHG1, FZD1, IFITM1, MUC20, KRT80, and SALL1) were filtered out using the random forest model. The model of Riskscore was obtained by multiplying the expression levels of these 12 genes with the corresponding coefficients of the multivariate regression. We found that the Riskscore correlated with the expression of these 12 genes; the high Riskscore matched the low survival rate verified in the verification set. The analysis found that the Riskscore model was associated with most of the metabolic processes, immune infiltration of cells such as plasma cells, immune checkpoints such as PD-1, and clinical characteristics such as M stage. Conclusion. We established a new Riskscore model for the prognosis of ccRCC based on metabolism. The genes in the model provided several novel targets for the study of ccRCC.

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“…ccRCC patients receiving anti-PD-1, the low m 6 Ascore group presented an apparently prolonged survival ( Zhong et al, 2021 ). Li H. et al (2021) further validated that a low m 6 Ascore in kidney renal clear cell carcinoma patients indicates an inflammatory phenotype and higher sensitivity to anticancer immunotherapy. Zhou et al (2021) also confirmed that m 6 Ascore-low pancreatic cancer patients have higher response rates to anti-PD-1 and anti-CTLA-4 treatments.…”

Section: Targeting M 6 a Rna Modification As Cancer Immunotherapymentioning

confidence: 65%

N6-Methyladenosine RNA Modification: An Emerging Immunotherapeutic Approach to Turning Up Cold Tumors

Zhan

Zhang

Zhu

et al. 2021

Front. Cell Dev. Biol.

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Immunotherapy is a novel clinical approach that has shown clinical efficacy in multiple cancers. However, only a fraction of patients respond well to immunotherapy. Immuno-oncological studies have identified the type of tumors that are sensitive to immunotherapy, the so-called hot tumors, while unresponsive tumors, known as “cold tumors,” have the potential to turn into hot ones. Therefore, the mechanisms underlying cold tumor formation must be elucidated, and efforts should be made to turn cold tumors into hot tumors. N6-methyladenosine (m6A) RNA modification affects the maturation and function of immune cells by controlling mRNA immunogenicity and innate immune components in the tumor microenvironment (TME), suggesting its predominant role in the development of tumors and its potential use as a target to improve cancer immunotherapy. In this review, we first describe the TME, cold and hot tumors, and m6A RNA modification. Then, we focus on the role of m6A RNA modification in cold tumor formation and regulation. Finally, we discuss the potential clinical implications and immunotherapeutic approaches of m6A RNA modification in cancer patients. In conclusion, m6A RNA modification is involved in cold tumor formation by regulating immunity, tumor-cell-intrinsic pathways, soluble inhibitory mediators in the TME, increasing metabolic competition, and affecting the tumor mutational burden. Furthermore, m6A RNA modification regulators may potentially be used as diagnostic and prognostic biomarkers for different types of cancer. In addition, targeting m6A RNA modification may sensitize cancers to immunotherapy, making it a promising immunotherapeutic approach for turning cold tumors into hot ones.

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RNA Modification of N6-Methyladenosine Predicts Immune Phenotypes and Therapeutic Opportunities in Kidney Renal Clear Cell Carcinoma

Cited by 30 publications

References 50 publications

N6-Methyladenosine in Cancer Immunotherapy: An Undervalued Therapeutic Target

N6-Methyladenosine in Cancer Immunotherapy: An Undervalued Therapeutic Target

Identification of Prognostic Metabolism-Related Genes in Clear Cell Renal Cell Carcinoma

N6-Methyladenosine RNA Modification: An Emerging Immunotherapeutic Approach to Turning Up Cold Tumors

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