A better understanding of the tumor immune microenvironment (TIME) in metastatic clear cell renal cell carcinoma (ccRCC) may help inform precision treatment strategies. We sought to identify clinically meaningful TIME signatures in ccRCC.
DESIGN: We studied tumors from 39 patients with metastatic ccRCC using quantitative multiplexed immunofluorescence and relevant immune marker panels. Cell densities were analyzed in 3 regions of interest (ROIs): tumor core, tumor-stroma interface, and stroma. Patients were stratified into low- and high-marker density groups using median values as thresholds. Log-rank and Cox regression analyses while controlling for clinical variables were used to compare survival outcomes to patterns of immune cell distributions.
There were significant associations with increased macrophage (CD68+ /CD163+ /CD206+ ) density and poor outcomes across multiple ROIs in primary and metastatic tumors. In primary tumors, T-Bet+ Th1 cell density was highest at the tumor-stromal interface (P = 0.0021), and increased coexpression of CD3 and T-Bet was associated with improved overall survival (P = 0.015) and survival after immunotherapy (P = 0.014). In metastatic tumor samples, decreased FOXP3+ T regulatory cell density correlated with improved survival after immunotherapy (P = 0.016).
Increased macrophage markers and decreased Th1 T cell markers within the TIME correlated with poor overall survival and treatment outcomes. Immune markers such as FOXP3 showed consistent levels across the TIME, whereas others such as T-bet, demonstrated significant variance across the distinct ROIs. These findings suggest that TIME profiling outside the tumor core may identify clinically relevant associations for patients with metastatic ccRCC.
Clinical and experimental immunology. 2020 Dec 21 [Epub ahead of print]
Ali Hajiran, Nick Chakiryan, Ahmet M Aydin, Logan Zemp, Jonathan Nguyen, Jose M Laborde, Jad Chahoud, Philippe E Spiess, Saif Zaman, Shayan Falasiri, Michelle Fournier, Jamie K Teer, Jasreman Dhillon, Susan McCarthy, Carlos Moran-Segura, Esther N Katende, Wade J Sexton, John M Koomen, James Mulé, Youngchul Kim, Brandon Manley
Department of Genitourinary Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA., Department of Pathology, H Lee Moffitt Cancer Center, Tampa, Florida, USA., Department of Biostatistics and Bioinformatics, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA., Department of Proteomics, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA., Department of Immunology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.