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From Bench to Bedside: How the Tumor Microenvironment Is Impacting the Future of Immunotherapy for Renal Cell Carcinoma.

ABSTRACT: Immunotherapy has revolutionized the treatment landscape for many cancer types. The treatment for renal cell carcinoma (RCC) has especially evolved in recent years, from cytokine-based immunotherapies to immune checkpoint inhibitors. Although clinical benefit from immunotherapy is limited to a subset of patients, many combination-based approaches have led to improved outcomes. The success of such approaches is a direct result of the tumor immunology knowledge accrued regarding the RCC microenvironment, which, while highly immunogenic, demonstrates many unique characteristics. Ongoing translational work has elucidated some of the mechanisms of response, as well as primary and secondary resistance, to immunotherapy. Here, we provide a comprehensive review of the RCC immunophenotype with a specific focus on how preclinical and clinical data are shaping the future of immunotherapy.

SUBMITTER: Anker J

PROVIDER: S-EPMC8619121 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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From Bench to Bedside: How the Tumor Microenvironment Is Impacting the Future of Immunotherapy for Renal Cell Carcinoma.

Anker Jonathan J Miller Justin J Taylor Nicole N Kyprianou Natasha N Tsao Che-Kai CK

Cells 20211119 11

Immunotherapy has revolutionized the treatment landscape for many cancer types. The treatment for renal cell carcinoma (RCC) has especially evolved in recent years, from cytokine-based immunotherapies to immune checkpoint inhibitors. Although clinical benefit from immunotherapy is limited to a subset of patients, many combination-based approaches have led to improved outcomes. The success of such approaches is a direct result of the tumor immunology knowledge accrued regarding the RCC microenvir ...[more]

PMID: 34831452

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Project description:Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer and has strong immunogenicity. A systematically investigation of the tumor microenvironment (TME) in ccRCC could contribute to help clinicians develop personalized treatment and facilitate clinical decision-making. In this study, we analyzed the immune-related subtype of ccRCC on the basis of immune-related gene expression data in The Cancer Genome Atlas (TCGA, N = 512) and E-MTAB-1980 (N = 101) dataset, respectively. As a result, two subtypes (C1 and C2) were identified by performing non-negative matrix factorization clustering. Subtype C1 was characterized by increased advance ccRCC cases and immune-related pathways. A higher immune score, stromal score, TMB value, Tumor Immune Dysfunction and Exclusion (TIDE) prediction score, and immune checkpoint genes expression level were also observed in C1. In addition, the C1 subtype might benefit from chemotherapy and immunotherapy. The patients in subtype C2 had more metabolism-related pathways, higher tumor purity, and a better prognosis. Moreover, some small molecular compounds for the treatment of ccRCC were identified between the two subtypes by using the Connectivity Map (CMap) database. Finally, we constructed and validated an immune-related (IR) score to evaluate immune modification individually. A high IR score corresponded to a favorable prognosis compared to a low IR score, while more advanced tumor stage and grade cases were enriched in the low IR score group. The two IR score groups also showed a distinct divergence among immune status, TME, and chemotherapy. The external validation dataset (E-MTAB-1980) and another immunotherapy cohort (IMvigor 210) demonstrated that patients in the high IR score group had a significantly prolonged survival time and clinical benefits compared to the low IR score group. Together, characterization of molecular heterogeneity and IR signature may help develop new insights into the TME of ccRCC and provide new strategies for personalized treatment.

Dataset Information

From Bench to Bedside: How the Tumor Microenvironment Is Impacting the Future of Immunotherapy for Renal Cell Carcinoma.

Publications

From Bench to Bedside: How the Tumor Microenvironment Is Impacting the Future of Immunotherapy for Renal Cell Carcinoma.

Similar Datasets

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