Strategies targeting tumor immune and stromal microenvironment and their clinical relevance

Hu, Mengying; Huang, Leaf

doi:10.1016/j.addr.2022.114137

Cited by 38 publications

(24 citation statements)

References 210 publications

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“…Increasing evidence has confirmed that the cellular and non-cellular components of the tumor microenvironment may impact the prognosis and treatment of HCC. A previous study of pathological sections of HCC patients showed that differential gene expression in tumor cells and their stroma has important implications for tumor survival and molecular subtypes ( Hu and Huang, 2022 ). Recently, immunotherapy provided advanced HCC patients with more options beyond targeted drugs.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of nine m7G-related lncRNAs as prognosis factors in tumor immune microenvironment of hepatocellular carcinoma and experimental validation

Wang

Zhou²,

Wang³

et al. 2022

Front. Genet.

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Background: Hepatocellular carcinoma (HCC) remains the most prevalent gastrointestinal malignancy worldwide, with robust drug resistance to therapy. N7-methylguanosine (m7G) mRNA modification has been significantly related to massive human diseases. Considering the effect of m7G-modified long non-coding RNAs (lncRNAs) in HCC progression is unknown, the study aims at investigating a prognostic signature to improve clinical outcomes for patients with HCC.Methods: Two independent databases (TCGA and ICGC) were used to analyze RNAseq data of HCC patients. First, co-expression analysis was applied to obtain the m7G-related lncRNAs. Moreover, consensus clustering analysis was employed to divide HCC patients into clusters. Then, using least absolute shrinkage and selection operator-Cox regression analysis, the m7G-related lncRNA prognostic signature (m7G-LPS) was first tested in the training set and then confirmed in both the testing and ICGC sets. The expression levels of the nine lncRNAs were further confirmed via real-time PCR in cell lines, principal component analysis, and receiver operating characteristic curve. The m7G-LPS could divide HCC patients into two different risk groups with the optimal risk score. Then, Kaplan–Meier curves, tumor mutation burden (TMB), therapeutic effects of chemotherapy agents, and expressions of immune checkpoints were performed to further enhance the availability of immunotherapeutic treatments for HCC patients.Results: A total of 1465 lncRNAs associated with the m7G genes were finally selected from the TCGA database, and through the univariate Cox regression, the expression levels of 22 m7G-related lncRNAs were concerning HCC patients’ overall survival (OS). Then, the whole patients were grouped into two subgroups, and the OS in Cluster 1 was longer than that of patients in Cluster 2. Furthermore, nine prognostic m7G-related lncRNAs were identified to conduct the m7G-LPS, which were further verified. A prognostic nomogram combined age, gender, HCC grade, stage, and m7G-LPS showed strong reliability and accuracy in predicting OS in HCC patients. Finally, immune checkpoint expression, TMB, and several chemotherapy agents were remarkably associated with risk scores. More importantly, the OS of the TMB-high patients was the worst among the four groups.Conclusion: The prognostic model we established was validated by abundant algorithms, which provided a new perspective on HCC tumorigenesis and thus improved individualized treatments for patients.

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Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of nine m7G-related lncRNAs as prognosis factors in tumor immune microenvironment of hepatocellular carcinoma and experimental validation

Wang

Zhou²,

Wang³

et al. 2022

Front. Genet.

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“…The critical role of TME is beyond doubt in tumor initiation and development. Although studies have facilitated the identification of the important functions of different immune cell subtypes within TME, the CD8 + T cell is the central focus in engaging adaptive immunity for cancer control according to the cancer-immunity cycle ( 14 , 55 ). Moreover, the number and functionality of CD8 + T cells after activation are prerequisites for the efficacy of immunotherapy in patients with lung cancer ( 56 ).…”

Section: Discussionmentioning

confidence: 99%

A robust CD8+ T cell-related classifier for predicting the prognosis and efficacy of immunotherapy in stage III lung adenocarcinoma

Feng

Xu²,

Zhang³

et al. 2022

Front. Immunol.

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Patients with stage III lung adenocarcinoma (LUAD) have significant survival heterogeneity, meanwhile, CD8+ T cell has a remarkable function in immunotherapy. Therefore, developing novel biomarkers based on CD8+ T cell can help evaluate the prognosis and guide the strategy of immunotherapy for patients with stage III LUAD. Thus, we abstracted twelve datasets from multiple online databases and grouped the stage III LUAD patients into training and validation sets. We then used WGCNA and CIBERSORT, while univariate Cox analysis, LASSO analysis, and multivariate Cox analysis were performed. Subsequently, a novel CD8+ T cell-related classifier including HDFRP3, ARIH1, SMAD2, and UPB1 was developed, which could divide stage III LUAD patients into high- and low-risk groups with distinct survival probability in multiple cohorts (all P < 0.05). Moreover, a robust nomogram including the traditional clinical parameters and risk signature was constructed, and t-ROC, C-index, and calibration curves confirmed its powerful predictive capacity. Besides, we detected the difference in immune cell subpopulations and evaluated the potential benefits of immunotherapy between the two risk subsets. Finally, we verified the correlation between the gene expression and CD8+ T cells included in the model by immunohistochemistry and validated the validity of the model in a real-world cohort. Overall, we constructed a robust CD8+ T cell-related risk model originally which could predict the survival rates in stage III LUAD. What’s more, this model suggested that patients in the high-risk group could benefit from immunotherapy, which has significant implications for accurately predicting the effect of immunotherapy and evaluating the prognosis for patients with stage III LUAD.

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“…In addition to targeting tumor cells directly, recent research has focused on the treatment of the tumor microenvironment (TME) as a whole [ 21 , 22 ]. The components of the TME, including various cell types, surrounding stroma, blood vessels and lymphatic vessels, and cytokines [ 23 ], provide a good material basis for the proliferation and metastasis of tumor cells and serve as barriers or chances for anti-cancer nanomedicines [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Tumor-on-a-chip model for advancement of anti-cancer nano drug delivery system

et al. 2022

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Despite explosive growth in the development of nano-drug delivery systems (NDDS) targeting tumors in the last few decades, clinical translation rates are low owing to the lack of efficient models for evaluating and predicting responses. Microfluidics-based tumor-on-a-chip (TOC) systems provide a promising approach to address these challenges. The integrated engineered platforms can recapitulate complex in vivo tumor features at a microscale level, such as the tumor microenvironment, three-dimensional tissue structure, and dynamic culture conditions, thus improving the correlation between results derived from preclinical and clinical trials in evaluating anticancer nanomedicines. The specific focus of this review is to describe recent advances in TOCs for the evaluation of nanomedicine, categorized into six sections based on the drug delivery process: circulation behavior after infusion, endothelial and matrix barriers, tumor uptake, therapeutic efficacy, safety, and resistance. We also discuss current issues and future directions for an end-use perspective of TOCs.

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Strategies targeting tumor immune and stromal microenvironment and their clinical relevance

Cited by 38 publications

References 210 publications

Comprehensive analysis of nine m7G-related lncRNAs as prognosis factors in tumor immune microenvironment of hepatocellular carcinoma and experimental validation

Comprehensive analysis of nine m7G-related lncRNAs as prognosis factors in tumor immune microenvironment of hepatocellular carcinoma and experimental validation

A robust CD8+ T cell-related classifier for predicting the prognosis and efficacy of immunotherapy in stage III lung adenocarcinoma

Tumor-on-a-chip model for advancement of anti-cancer nano drug delivery system

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