Characterizing the tumor microenvironment in rare renal cancer histological types

Abstract

The tumor microenvironment (TME), including immune cells, cancer-associated fibroblasts, endothelial cells, adjacent normal cells, and others, plays a crucial role in influencing tumor behavior and progression. Here, we characterized the TME in 83 primary renal tumors and matched metastatic or recurrence tissue samples (n = 15) from papillary renal cell carcinoma (pRCC) types 1 (n = 20) and 2 (n = 49), collecting duct carcinomas (CDC; n = 14), and high-grade urothelial carcinomas (HGUC; n = 5). We investigated 10 different markers of immune infiltration, vasculature, cell proliferation, and epithelial-to-mesenchymal transition by using machine learning image analysis in conjunction with immunohistochemistry. Marker expression was compared by Mann-Whitney and Kruskal-Wallis tests and correlations across markers using Spearman's rank correlation coefficient. Multivariable Poisson regression analysis was used to compare marker expression between histological types, while accounting for variation in tissue size. Several immune markers showed different rates of expression across histological types of renal carcinoma. Using pRCC1 as reference, the incidence rate ratio (IRR) of CD3+ T cells (IRR [95% confidence interval, CI] = 2.48 [1.53-4.01]) and CD20+ B cells (IRR [95% CI] = 4.38 [1.22-5.58]) was statistically significantly higher in CDC. In contrast, CD68+ macrophages predominated in pRCC1 (IRR [95% CI] = 2. 35 [1.42-3.9]). Spatial analysis revealed CD3+ T-cell and CD20+ B-cell expressions in CDC to be higher at the proximal (p < 0.0001) and distal (p < 0.0001) tumor periphery than within the central tumor core. In contrast, expression of CD68+ macrophages in pRCC2 was higher in the tumor center compared to the proximal (p = 0.0451) tumor periphery and pRCC1 showed a distance-dependent reduction, from the central tumor, in CD68+ macrophages with the lowest expression of CD68 marker at the distal tumor periphery (p = 0.004). This study provides novel insights into the TME of rare kidney cancer types, which are often understudied. Our findings of differences in marker expression and localization by histological subtype could have implications for tumor progression and response to immunotherapies or other targeted therapies.

The application of 3D bioprinting in urological diseases

“…Clinical treatment with immune checkpoint inhibitors in combination with anti-angiogenic therapies has demonstrated positive effects on the clinical outcomes for patients with ccRCC, suggesting that the TME facilitates renal cancer development [ 182 ]. The TME of more aggressive renal cancers, like papillary RCC (pRCC) and collecting duct carcinomas, was also analyzed and found to have different marker expression for immune infiltration, vasculature, cell proliferation, and epithelial-to-mesenchymal (EMT) transition [ 183 ]. Therefore, the influence of TME in renal cancer should be more seriously considered in clinical treatment and better investigated to promote personalized therapies (See Table 3 ).…”

SAA1 Has Potential as a Prognostic Biomarker Correlated with Cell Proliferation, Migration, and an Indicator for Immune Infiltration of Tumor Microenvironment in Clear Cell Renal Cell Carcinoma

“…Recent research has found that the complex heterogeneity of the renal tumor was reflected in the composition of the TME. The tumor core of papillary renal cell carcinoma was mainly enriched with macrophages, while the periphery of collecting duct carcinoma was mostly rich in B cells and CD3+ T cells [ 46 ]. Although TME existed heterogeneity, one study identified the core immune-related genes (IGLL5 and IL2RA) in ccRCC and papillary renal cell carcinoma [ 47 ].…”

Speckle-type POZ protein could play a potential inhibitory role in human renal cell carcinoma

“…Tumor-adjacent renal tissue may have oncological relevance,that the tumor progression or local recurrence may be associated with the molecular status of the tumor adjacent tissue [ 52 , 53 ]. The tumor microenvironment (TME), including immune cells,adjacent normal cells and so on plays a crucial role in influencing tumor behavior and progression [ 54 ]. Some interesting yet complex events occur at tumor borders that contribute to the aberrant molecular changes occurring in adjacent renal tissue.…”