Dataset Information

Tumor Microenvironment Features as Predictive Biomarkers of Response to Immune Checkpoint Inhibitors (ICI) in Metastatic Clear Cell Renal Cell Carcinoma (mccRCC).

ABSTRACT: Renal cell carcinoma (RCC) is the seventh most frequently diagnosed malignancy with an increasing incidence in developed countries. Despite a greater understanding of the cancer biology, which has led to an increase of therapeutic options, metastatic clear cell renal cell carcinoma (mccRCC) still have a poor prognosis with a median five-years survival rate lower than 10%. The standard of care for mccRCC has changed dramatically over the past decades with the emergence of new treatments: anti-VEGFR tyrosine kinase inhibitors, mTOR Inhibitors and immune checkpoint inhibitors (ICI) such as anti-Programmed cell-Death 1 (PD-1) and anti-anti-Programmed Death Ligand-1 (PD-L1) used as monotherapy or as a combination with anti CTLA-4 or anti angiogenic therapies. In the face of these rising therapeutic options, the question of the therapeutic sequences is crucial. Predictive biomarkers are urgently required to provide a personalized treatment for each patient. Disappointingly, the usual ICI biomarkers, PD-L1 expression and Tumor Mutational Burden, approved in melanoma or non-small cell lung cancer (NSCLC) have failed to distinguish good and poor mccRCC responders to ICI. The tumor microenvironment is known to be involved in ICI response. Innovative technologies can be used to explore the immune contexture of tumors and to find predictive and prognostic biomarkers. Recent comprehensive molecular characterization of RCC has led to the development of robust genomic signatures, which could be used as predictive biomarkers. This review will provide an overview of the components of the RCC tumor microenvironment and discuss their role in disease progression and resistance to ICI. We will then highlight the current and future ICI predictive biomarkers assessed in mccRCC with a major focus on immunohistochemistry markers and genomic signatures.

SUBMITTER: Simonaggio A

PROVIDER: S-EPMC7827724 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Tumor Microenvironment Features as Predictive Biomarkers of Response to Immune Checkpoint Inhibitors (ICI) in Metastatic Clear Cell Renal Cell Carcinoma (mccRCC).

Simonaggio Audrey A Epaillard Nicolas N Pobel Cédric C Moreira Marco M Oudard Stéphane S Vano Yann-Alexandre YA

Cancers 20210110 2

Renal cell carcinoma (RCC) is the seventh most frequently diagnosed malignancy with an increasing incidence in developed countries. Despite a greater understanding of the cancer biology, which has led to an increase of therapeutic options, metastatic clear cell renal cell carcinoma (mccRCC) still have a poor prognosis with a median five-years survival rate lower than 10%. The standard of care for mccRCC has changed dramatically over the past decades with the emergence of new treatments: anti-VEG ...[more]

PMID: 33435262

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Project description:Background: It is anticipated that there will be a large rise in the number of tumor diagnoses and mortality in those aged 65 and older over the course of upcoming decades. Immune checkpoint inhibitors, often known as ICIs, boost immune system activity by selectively targeting ICI genes. On the other hand, old age may be connected with unfavorable results. Methods: The Cancer Genome Atlas (TCGA) provided gene expression data from ccRCC tissue and key clinical variables. ICI gene databases were applied and verified using the GEO database. Results: We identified 14 ICI genes as risk gene signatures among 528 ccRCC patients using univariate and multivariable cox hazard models, and the elderly group was linked with poor survival. Then, by utilizing a new nomogram method, the TNFSF15 gene and age predicting values were estimated at one, three, and five years (85%, 81%, and 81%), respectively, and our age-related risk score was significant even after multivariable analysis (HR = 1.518, p = 0.009, CI = 1.1102.076). TNFSF15 gene expression was lower in elderly ccRCC patients (p = 0.0001). A negative connection between age and the TNFSF15 gene expression was discovered by correlation analysis (p = 0.0001). The verification of the gene by utilizing GEO (GSE167093) with 604 patients was obtained as external validation that showed significant differences in the TNFSF15 gene between young and elderly patients (p = 0.007). Additionally, the protein-protein interactions of the TNFSF15 gene with other ICI genes and aging-related genes was determined. In addition, the TNFSF15 expression was significantly correlated with pathological stages (p = 0.018). Furthermore, it was discovered that the biological processes of senescence, cellular senescence, the immune system, and many immune cell infiltration and immune function types are all closely tied. Conclusions: Along with the risk score evaluation, the ICI gene TNFSF15 was identified as a tumor suppressor gene related to inequalities in age survival and is associated with pathological stages and different immunity statuses. The aging responses of ccRCC patients and related gene expression need further investigation in order to identify potential therapeutic targets.

Dataset Information

Tumor Microenvironment Features as Predictive Biomarkers of Response to Immune Checkpoint Inhibitors (ICI) in Metastatic Clear Cell Renal Cell Carcinoma (mccRCC).

Publications

Tumor Microenvironment Features as Predictive Biomarkers of Response to Immune Checkpoint Inhibitors (ICI) in Metastatic Clear Cell Renal Cell Carcinoma (mccRCC).

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