학술논문
Analysis of the Tumor Immune Microenvironment (TIME) in Clear Cell Renal Cell Carcinoma (ccRCC) Reveals an M0 Macrophage-Enriched Subtype: An Exploration of Prognostic and Biological Characteristics of This Immune Phenotype
Document Type
Academic Journal
Author
Source
Cancers. November 2023, Vol. 15 Issue 23
Subject
Language
English
ISSN
2072-6694
Abstract
Author(s): Mark Farha [1]; Srinivas Nallandhighal [2]; Randy Vince [2]; Brittney Cotta [2]; Judith Stangl-Kremser [2,3]; Daniel Triner [2]; Todd M. Morgan [2,4]; Ganesh S. Palapattu [1,2,3,4]; Marcin Cieslik [4,5,6]; [...]
Until recently, checkpoint inhibitors have largely been reserved for the metastatic disease space in clear cell renal cell carcinoma (ccRCC). Over the last several years, a growing body of trials have investigated the application of checkpoint inhibitor therapy in the neoadjuvant and adjuvant settings. However, these trials have yielded mixed results, due largely in part to a lack of high-fidelity biomarkers for patient selection and response prediction. Here, we present a simple workflow leveraging genomic data to characterize the immune microenvironment in ccRCC and identify a key macrophage subset that is associated with aggressive tumor biology, poor prognosis, and decreased response to immune checkpoint blockade (ICB). This work lays the foundation for future mechanistic discovery and prospective validation of integrating macrophage content into a ccRCC immune checkpoint blockade biomarker strategy. There is a need to optimize the treatment of clear cell renal cell carcinoma (ccRCC) patients at high recurrence risk after nephrectomy. We sought to elucidate the tumor immune microenvironment (TIME) of localized ccRCC and understand the prognostic and predictive characteristics of certain features. The discovery cohort was clinically localized patients in the TCGA-Kidney Renal Clear Cell Carcinoma (KIRC) project (n = 382). We identified an M0 macrophage-enriched cluster (n = 25) in the TCGA-KIRC cohort. This cluster’s median progression-free survival (PFS) and overall survival (OS) were 40.4 and 45.3 months, respectively, but this was not reached in the others (p = 0.0003 and
Until recently, checkpoint inhibitors have largely been reserved for the metastatic disease space in clear cell renal cell carcinoma (ccRCC). Over the last several years, a growing body of trials have investigated the application of checkpoint inhibitor therapy in the neoadjuvant and adjuvant settings. However, these trials have yielded mixed results, due largely in part to a lack of high-fidelity biomarkers for patient selection and response prediction. Here, we present a simple workflow leveraging genomic data to characterize the immune microenvironment in ccRCC and identify a key macrophage subset that is associated with aggressive tumor biology, poor prognosis, and decreased response to immune checkpoint blockade (ICB). This work lays the foundation for future mechanistic discovery and prospective validation of integrating macrophage content into a ccRCC immune checkpoint blockade biomarker strategy. There is a need to optimize the treatment of clear cell renal cell carcinoma (ccRCC) patients at high recurrence risk after nephrectomy. We sought to elucidate the tumor immune microenvironment (TIME) of localized ccRCC and understand the prognostic and predictive characteristics of certain features. The discovery cohort was clinically localized patients in the TCGA-Kidney Renal Clear Cell Carcinoma (KIRC) project (n = 382). We identified an M0 macrophage-enriched cluster (n = 25) in the TCGA-KIRC cohort. This cluster’s median progression-free survival (PFS) and overall survival (OS) were 40.4 and 45.3 months, respectively, but this was not reached in the others (p = 0.0003 and