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.
Highlights
Papillary renal cell carcinoma (PRCC) is the second most common histological subtype of renal cell carcinoma after the clear cell subtype, where it accounts for 15% to 20% of kidney cancers [1]
The gene expression matrix and related clinical information for 136 PRCC tissues were downloaded from The Cancer Genome Atlas (TCGA)
After dividing tumor tissues into type 1 and type 2 PRCC, the result showed that immune scores and stromal scores were associated with overall survival in patients with type 2 PRCC rather than type 1 PRCC (Figures 1(b) and 1(c))
Summary
Papillary renal cell carcinoma (PRCC) is the second most common histological subtype of renal cell carcinoma after the clear cell subtype, where it accounts for 15% to 20% of kidney cancers [1]. Type 1 and type 2 PRCC are shown to be different types of renal cancer with distinct histologic features and diverse clinical prognosis. Compared with type 1 PRCC, type 2 PRCC is more heterogeneous and aggressive which is associated with higher mortality. Successful treatment is challenging after metastasis occurs because the targeted drugs are generally less robust [2]. The drug resistance mechanism remains unclear, and there is no standard therapy for metastatic PRCC patients at present. PRCC has attracted increasing attention recently, especially in the field of immunotherapy
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