Beyond Tumor Mutation Burden: Tumor Neoantigen Burden as a Biomarker for Immunotherapy and Other Types of Therapy

Wang, Peipei; Chen, Yueyun; Wang, Chun

doi:10.3389/fonc.2021.672677

Cited by 62 publications

(54 citation statements)

References 106 publications

(98 reference statements)

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“…However, because of the low toxicity of immunotherapy, the exploration of immunotherapy approaches for WT has never stopped. 35 , 38 Therefore, it was hoped that our study could bring some ideas for the follow‐up research of WT.…”

Section: Discussionmentioning

confidence: 96%

Myelin and lymphocyte protein serves as a prognostic biomarker and is closely associated with the tumor microenvironment in the nephroblastoma

Huang

et al. 2022

Cancer Medicine

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Nephroblastoma, also known as Wilms' tumor (WT), is the most common renal tumor that occurs in children. Although the efficacy of treatment has been significantly improved by a series of comprehensive treatments, some patients still have poor prognosis. Myelin and lymphocyte (MAL) protein, a highly hydrophobic integrated membrane‐bound protein, has been implicated in many tumors and is also closely linked to kidney development. However, the relationship between MAL and WT has not yet been elucidated. Therefore, we attempted to evaluate the feasibility of MAL as a promising prognosis factor for WT. The differential expression of MAL was investigated using TARGET database and was verified using the Gene Expression Omnibus database and real‐time quantitative PCR. The prognostic ability of MAL was determined using Kaplan–Meier and Cox regression analyses. Pearson correlation analysis was applied to explore the relationship between MAL expression and methylation sites. The ESTIMATE and CIBERSORT algorithms showed that MAL expression was associated with the WT tumor microenvironment. Gene Set Enrichment Analysis (GSEA) indicated that multiple signaling pathways closely associated with tumorigenesis were differentially enriched between the high‐ and low‐MAL groups. In conclusion, our study comprehensively explored the potential of MAL as a prognosis factor for WT. Meanwhile, we also demonstrated that MAL, as a prognostic factor for WT, may be closely related to the tumor microenvironment.

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Section: Discussionmentioning

confidence: 96%

Myelin and lymphocyte protein serves as a prognostic biomarker and is closely associated with the tumor microenvironment in the nephroblastoma

Huang

et al. 2022

Cancer Medicine

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“…In addition, using the somatic mutation data available in the TCGA cohort, we found obviously lower TMB in the high-risk group. It has been reported that tumors with low TMB generates fewer neoantigens, thus avoiding being attacked by CTLs ( Wang et al, 2021b ). Taken together, these findings suggested the important role of IRLPS in determining TME cell infiltration and predicting response to ICB therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Given that tumor mutation burden (TMB) has emerged as a promising biomarker for predicting the immunotherapeutic response, we also calculated the TMB of GC patients in the TCGA cohort. TMB was defined as the total number of nonsynonymous mutations per megabase in the coding area of a tumor genome ( Wang et al, 2021b ). The “maftools” and “GenVisR” R packages were used to analyze and visualize common mutations ( Skidmore et al, 2016 ; Mayakonda et al, 2018 ).…”

Section: Methodsmentioning

confidence: 99%

Comprehensive Analysis of an Individualized Immune-Related lncRNA Pair Signature in Gastric Cancer

Nie

Zhai

Wang

et al. 2022

Front. Cell Dev. Biol.

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Long noncoding RNAs (lncRNAs) have diverse functions, including immune regulation. Increasing studies have reported immune-related lncRNAs in the prognosis of multiple cancers. In this study, we developed an individualized signature containing 13 immune-related lncRNA pairs (IRLPs) which could predict the overall survival, disease-free survival, progression-free survival, and disease-specific survival of gastric cancer (GC) patients in The Cancer Genome Atlas (TCGA) cohort, and internal and external validations, signature comparisons, and subgroup analyses further confirmed its superiority, stability, and generalizability. Notably, this signature also showed good applicability in discriminating the prognosis of pan-cancer patients. Then, we constructed and validated a nomogram for overall survival based on the signature and clinical factors, which allowed more accurate predictions of GC prognosis. In addition, we revealed that the low survival rate of patients with high-risk scores may be due to their aggressive clinical features, enriched cancer-related signaling pathways, the infiltration of specific immunosuppressive cells, and low tumor mutation burden. We further predicted obviously worse immunotherapeutic responses in the high-risk groups and identified some candidate compounds targeting GC risk group differentiation. This signature based on the IRLPs may be promising for predicting the survival outcomes and immunotherapeutic responses of GC patients in clinical practice.

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“…Increased neoantigen load renders the tumor immunogenic with increased infiltration of lymphocytes leading to better clinical response to ICI in non-small cell lung cancer, melanoma, colorectal adenocarcinoma ( 185 ). In a breast cancer model, recent research from our group found that tumor hypoxia increased tumor mutational load and potential neoantigens ( 186 ).…”

Section: The Hidden Potential Of Hypoxia-modulated Genetic Heterogene...mentioning

confidence: 99%

The Effect of Hypoxia and Hypoxia-Associated Pathways in the Regulation of Antitumor Response: Friends or Foes?

et al. 2022

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Hypoxia is an environmental stressor that is instigated by low oxygen availability. It fuels the progression of solid tumors by driving tumor plasticity, heterogeneity, stemness and genomic instability. Hypoxia metabolically reprograms the tumor microenvironment (TME), adding insult to injury to the acidic, nutrient deprived and poorly vascularized conditions that act to dampen immune cell function. Through its impact on key cancer hallmarks and by creating a physical barrier conducive to tumor survival, hypoxia modulates tumor cell escape from the mounted immune response. The tumor cell-immune cell crosstalk in the context of a hypoxic TME tips the balance towards a cold and immunosuppressed microenvironment that is resistant to immune checkpoint inhibitors (ICI). Nonetheless, evidence is emerging that could make hypoxia an asset for improving response to ICI. Tackling the tumor immune contexture has taken on an in silico, digitalized approach with an increasing number of studies applying bioinformatics to deconvolute the cellular and non-cellular elements of the TME. Such approaches have additionally been combined with signature-based proxies of hypoxia to further dissect the turbulent hypoxia-immune relationship. In this review we will be highlighting the mechanisms by which hypoxia impacts immune cell functions and how that could translate to predicting response to immunotherapy in an era of machine learning and computational biology.

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Beyond Tumor Mutation Burden: Tumor Neoantigen Burden as a Biomarker for Immunotherapy and Other Types of Therapy

Cited by 62 publications

References 106 publications

Myelin and lymphocyte protein serves as a prognostic biomarker and is closely associated with the tumor microenvironment in the nephroblastoma

Myelin and lymphocyte protein serves as a prognostic biomarker and is closely associated with the tumor microenvironment in the nephroblastoma

Comprehensive Analysis of an Individualized Immune-Related lncRNA Pair Signature in Gastric Cancer

The Effect of Hypoxia and Hypoxia-Associated Pathways in the Regulation of Antitumor Response: Friends or Foes?

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