YTHDF2 correlates with tumor immune infiltrates in lower-grade glioma

Lin, Xinhua; Wang, Zhichao; Yang, Guangda; Wen, Guohua; Zhang, Ye

doi:10.18632/aging.103812

Cited by 21 publications

(20 citation statements)

References 84 publications

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“…Our study found that YTHDF2 was significantly related to LGG patients' overall survival (p < 0.001). A recent study has demonstrated that YTHDF2 acts as a potential biomarker that correlated with the LGG-infiltrating immune cells (Lin et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Pan-Cancer Prognostic, Immunity, Stemness, and Anticancer Drug Sensitivity Characterization of N6-Methyladenosine RNA Modification Regulators in Human Cancers

Yin

et al. 2021

Front. Mol. Biosci.

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N6-methyladenosine RNA modification plays a significant role in the progression of multiple tumorigenesis. Our study identified the imperative role of m6A regulators in the tumor immune microenvironment, survival, stemness score, and anticancer drug sensitivity of pan-cancer. The Wilcox test was to identify the differential expression between 17 m6A regulators across 33 TCGA cancer types and their normal tissues from UCSC Xena GDC pan-cancer. Survival analysis of m6A-related regulators in 33 TCGA cancer types was identified using the “survival” and “survminer” package. The Spearman correlation test and Pearson correlation test were used to identify the correlation relationship between m6A regulators expression and tumor microenvironment, tumor stem cell score, and drug sensitivity of anticancer drugs. ConsensusPathDB was used for exploring m6A regulators functional enrichment. The 17 (METTL3, WTAP, METTL14, RBM15, RBM15B, VIRMA, HNRNPC, HNRNPA2B1, YTHDC1, ZC3H13, YTHDF1, YTHDC2, YTHDF2, IGF2BP3, IGF2BP1, FTO, and ALKBH5) m6A regulators were differentially expressed in 18 TCGA cancer types and adjacent normal tissues. Correlation analysis indicated that the relationship between the expression of 17 m6A regulators and tumor microenvironment indicated that the higher expression of m6A regulators, the higher the degree of tumor stem cells. The anticancer drug sensitivity analysis indicated that ZC3H13 expression had a positive relationship with anticancer drugs such as selumetinib, dabrafenib, cobimetinib, trametinib, and hypothemycin (p < 0.001). YTHDF2 expression was significantly negatively correlated with the anticancer drug dasatinib (p < 0.001). The pan-cancer immune subtype analysis showed that the 17 m6A regulators were significantly different in immune subtype C1 (wound healing), C3 (inflammatory), C2 (IFN-gamma dominant), C5 (immunological quiet), C4 (lymphocyte depleted), and C6 (TGF-beta dominant) (p < 0.001). Our study provides a comprehensive insight for revealing the significant role of m6A regulators in the tumor immune microenvironment, stemness score, and anticancer drug sensitivity of human cancers.

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Section: Discussionmentioning

confidence: 99%

Pan-Cancer Prognostic, Immunity, Stemness, and Anticancer Drug Sensitivity Characterization of N6-Methyladenosine RNA Modification Regulators in Human Cancers

Yin

et al. 2021

Front. Mol. Biosci.

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“…Moreover, Garzon-Muvdi et al, 2018, have supported the prominence of DC activation in enhancing the efficacy of anti-PD-1 immunotherapy against glioblastoma [ 16 ]. Taken together, this study reveals the importance of targeting YTHDF2 in combination with DC-immunotherapy [ 7 ] to enhance the efficacy of ICB therapy against early stage brain tumors [ 15 ], ( Table 3 ).…”

Section: Epitranscriptomics In Icb-therapeuticsmentioning

confidence: 91%

“…Lin et al, 2020 [ 15 ] demonstrated the role of YTHDF2 in progression of lower-grade glioma (LGG) also called ‘pilocytic astrocytoma’, a type of early stage brain tumor. They showed that YTHDF2 is abnormally expressed in various types of cancers and reduces overall longevity and survival.…”

Section: Epitranscriptomics In Icb-therapeuticsmentioning

confidence: 99%

“…The higher expression of YTHDF2 has been positively correlated with immune cell (B-cells, T-cells, DCs, MΦ and neutrophils) expressing PD-1, TIM-3 and CTLA-4 markers. Therefore, targeting YTHDF2 in DCs would hold the potential to enhance anti-tumor immunity in combination with ICB-therapeutics [ 14 , 15 ]. A similar pre-clinical trial was proposed by jubilant-therapeutics targeting PD-1 inhibitor (with brain penetrant PRMT5) in controlling LGG, potentiating the scope to utilize in combinations with immune cells targeting intracellular checkpoints as targeted therapy.…”

Section: Epitranscriptomics In Icb-therapeuticsmentioning

confidence: 99%

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Epitranscriptomic Approach: To Improve the Efficacy of ICB Therapy by Co-Targeting Intracellular Checkpoint CISH

Kumar

Sarthi

Mani

et al. 2021

Cells

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Cellular immunotherapy has recently emerged as a fourth pillar in cancer treatment co-joining surgery, chemotherapy and radiotherapy. Where, the discovery of immune checkpoint blockage or inhibition (ICB/ICI), anti-PD-1/PD-L1 and anti-CTLA4-based, therapy has revolutionized the class of cancer treatment at a different level. However, some cancer patients escape this immune surveillance mechanism and become resistant to ICB-therapy. Therefore, a more advanced or an alternative treatment is required urgently. Despite the functional importance of epitranscriptomics in diverse clinico-biological practices, its role in improving the efficacy of ICB therapeutics has been limited. Consequently, our study encapsulates the evidence, as a possible strategy, to improve the efficacy of ICB-therapy by co-targeting molecular checkpoints especially N6A-modification machineries which can be reformed into RNA modifying drugs (RMD). Here, we have explained the mechanism of individual RNA-modifiers (editor/writer, eraser/remover, and effector/reader) in overcoming the issues associated with high-dose antibody toxicities and drug-resistance. Moreover, we have shed light on the importance of suppressor of cytokine signaling (SOCS/CISH) and microRNAs in improving the efficacy of ICB-therapy, with brief insight on the current monoclonal antibodies undergoing clinical trials or already approved against several solid tumor and metastatic cancers. We anticipate our investigation will encourage researchers and clinicians to further strengthen the efficacy of ICB-therapeutics by considering the importance of epitranscriptomics as a personalized medicine.

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“…The higher expression of YTHDF2 has been positively correlated with immune cell (B-cells, T-cells, DCs, MΦ and neutrophils) expressing PD-1, TIM-3 and CTLA-4 markers. Therefore, targeting YTHDF2 in DCs would hold the potential to enhance anti-tumor immunity in combination with ICB-therapeutics [74,76]. A similar pre-clinical trial was proposed by jubilant-therapeutics targeting PD-1 inhibitor (with brain penetrant PRMT5) in controlling LGG, potentiating the scope to utilize in combinations with immune cells targeting intracellular checkpoints as targeted therapy.…”

Section: Ythdf1 In Anti-pd1 Resistance (Solid Tumors)mentioning

confidence: 99%

Epitranscriptomic Approach: To Improve the Efficacy of ICB Therapy by Co-targeting Intracellular Checkpoint CISH

Kumar¹,

Sarthi²,

Mani³

et al. 2021

Preprint

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Cellular immunotherapy has recently emerged as a fourth pillar in cancer treatment co-joining surgery, chemotherapy and radiotherapy. Where, the discovery of immune checkpoint blockage or inhibition (ICB/ICI), anti-PD-1/PD-L1 and anti-CTLA4-based, therapy has revolutionized the class of cancer treatment at a different level. However, still some cancer patient escape this immune surveillance mechanism and become resistant to ICB-therapy. Therefore, a more advanced or an alternative treatment is required instantly. Despite the functional importance of epitranscriptomics in diverse clinico-biological practices, its role in improving the efficacy of ICB therapeutics has been limited. Consequently, our study encapsulates the evidences, as a possible strategy, to improve the efficacy of ICB-therapy by co-targeting molecular checkpoints especially N6A-modification machineries which could be reformed into RNA modifying drugs (RMD). Here, we have explained the mechanism of individual RNA-modifiers (editor/writer, eraser/remover and effector/reader) in overcoming the issues associated with high-dose antibody toxicities and drug-resistance. Moreover, we have shed light on the importance of suppressor of cytokine signalling (SOCS/CISH) and microRNAs in improving the efficacy of ICB-therapy, with brief insight on the current monoclonal antibodies undergoing clinical trials or already approved against several solid tumor and metastatic cancers. We anticipate our investigation will encourage researchers and clinicians to further strengthen the efficacy of ICB-therapeutics by considering the importance of epitranscriptomics as a personalized medicine.

show abstract

YTHDF2 correlates with tumor immune infiltrates in lower-grade glioma

Cited by 21 publications

References 84 publications

Pan-Cancer Prognostic, Immunity, Stemness, and Anticancer Drug Sensitivity Characterization of N6-Methyladenosine RNA Modification Regulators in Human Cancers

Pan-Cancer Prognostic, Immunity, Stemness, and Anticancer Drug Sensitivity Characterization of N6-Methyladenosine RNA Modification Regulators in Human Cancers

Epitranscriptomic Approach: To Improve the Efficacy of ICB Therapy by Co-Targeting Intracellular Checkpoint CISH

Epitranscriptomic Approach: To Improve the Efficacy of ICB Therapy by Co-targeting Intracellular Checkpoint CISH

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