Document Type
Article
Publication Date
7-2025
Identifier
DOI: 10.1177/24684562251358595
Abstract
Background
Papillary renal cell carcinoma (pRCC) is the second most common kidney cancer subtype, yet our understanding of its tumor immune microenvironment (TIME) remains limited.Objective
We utilized multiplex immunofluorescence (mIF) and spatial transcriptomics (ST) to evaluate immune cell architecture in pRCC contrasted with clear cell RCC (ccRCC).Methods
Localized RCC tumors (16 pRCC, 70 ccRCC) underwent mIF using markers for T cells, B cells, and tumor-associated macrophages (TAMs). Spatial data in both tumor and stromal compartments of the TIME were collected. A post hoc recurrence free survival analysis (RFS) was performed using Cox proportional hazard models. Single-cell ST was performed on a subset of samples, utilizing probes against 960 transcripts. Cell density, cell spatial clustering, and spatially varying gene expression were analyzed.Results
Immune cell density was statistically lower in pRCC amongst functional CD8T cells, while cell clustering was higher amongst M2-like macrophages. Using ST, two genes (CCL18, GPNMB) were enriched in clustered M2-like macrophages in pRCC (FDR < 0.001) and are known markers of lipid-associated TAMs (LAMs).Conclusion
Compared to ccRCC, pRCC has greater M2-like macrophage clustering. Using ST, M2-like macrophage clustering corresponds with lipid associated TAMs (LAMs), and therapeutics against this myeloid subset are currently being tested in pRCC.Journal Title
Kidney Cancer
Volume
9
First Page
24
Last Page
34
Keywords
multiplex immunofluorescence, papillary renal cell carcinoma, spatial biology, spatial transcriptomics, tumor associated macrophages, tumor immune microenvironment
Recommended Citation
Hayes MT, Laborde J, Soupir A, et al. Spatial clustering of immunosuppressive macrophages in papillary renal cell carcinoma. Kidney Cancer. 2025;9:24-34. doi:10.1177/24684562251358595
COinS
Comments
This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).
Publisher's Link: https://journals.sagepub.com/doi/full/10.1177/24684562251358595