Immune Cell Infiltration and Identifying Genes of Prognostic Value in the Papillary Renal Cell Carcinoma Microenvironment by Bioinformatics Analysis

Abstract

Papillary renal cell carcinoma (PRCC) is one of the most common histological subtypes of renal cell carcinoma. Type 1 and type 2 PRCC are reported to be clinically and biologically distinct. However, little is known about immune infiltration and the expression patterns of immune-related genes in these two histologic subtypes, thereby limiting the development of immunotherapy for PRCC. Thus, we analyzed the expression of 22 immune cells in type 1 and type 2 PRCC tissues by combining The Cancer Genome Atlas (TCGA) database with the ESTIMATE and CIBERSORT algorithms. Subsequently, we extracted a list of differentially expressed genes associated with the immune microenvironment. Multichip mRNA microarray data sets for PRCC were downloaded from the Gene Expression Omnibus (GEO) to further validate our findings. We found that the immune scores and stromal scores were associated with overall survival in patients with type 2 PRCC rather than type 1 PRCC. Tumor-infiltrating M1 and M2 macrophages could predict the clinical outcome by reflecting the host’s immune capacity against type 2 PRCC. Furthermore, CCL19/CCR7, CXCL12/CXCR4, and CCL20/CCR6 were shown to be potential new targets for tumor gene therapy in type 2 PRCC. Our findings provide valuable resources for improving immunotherapy for PRCC.

Characterizing the tumor microenvironment in rare renal cancer histological types

“…In our study, although not statically significant, pRCC2 expressed the highest median levels of CD163 (Figure 2) [34]. Consistent findings were seen at a transcriptomic level by Liu et al [35], based on CIBERSORT analysis, in which they found that M1 and M2 macrophages could predict pRCC2 clinical outcome. Thus, when creating a treatment plan for these cancer types, the pro-tumorigenic presence of M2 macrophages and the low expression levels of Tcell and B-cell markers should be considered.…”

Integrated Multi-Omics Analysis Identified PTPRG and CHL1 as Key Regulators of Immunophenotypes in Clear Cell Renal Cell Carcinoma(ccRCC)

“…According to these characteristic variations, we further divided cluster A into subcluster A1 and A2 while cluster B into B1 and B2 and the differences of PD-L1, IFN-γ expression levels and immune cells infiltration rates were even greater between subcluster A1 and B1 ( Figures 2B and 3A ). Considering previous studies demonstrated M2 macrophages were negatively related to overall survival and CD8 + T cells played a major role in anti-tumor immunity ( 17 – 19 ), we thus defined subcluster A1 as high cytotoxic immune phenotype while subcluster B1 as low cytotoxic immune phenotype. In our data, the contents of CD8 + T cells are negatively correlated with those of Macrophages M2, while in several previous studies the contents of CD8 + T cells were believed to predict a better survival benefit in multiple tumor types, Macrophages, however, in the opposite side ( 20 – 23 ).…”

Identification of CCL19 as a Novel Immune-Related Biomarker in Diabetic Nephropathy

“…CCL19 is a critical component of an immune-related prognostic classifier for the prognostic evaluation of patients with papillary renal cell carcinoma ( Wang et al, 2021 ). In addition, the CCL19/CCR7 axis could be a promising target for tumor gene therapy in type 2 papillary renal cell carcinoma according to Liu et al ’s report ( Liu et al, 2020 ). All the evidence demonstrates that CCL19 might be a critical biomarker and therapeutic target in human kidney diseases.…”