| Autor: |
Nicholas H Chakiryan, Youngchul Kim, Anders Berglund, Andrew Chang, Gregory J Kimmel, Ali Hajiran, Jonathan Nguyen, Carlos Moran-Segura, Daryoush Saeed-Vafa, Esther N Katende, Neale Lopez-Blanco, Jad Chahoud, Phillip Rappold, Philippe E Spiess, Michelle Fournier, Daniel Jeong, Liang Wang, Jamie K Teer, Jasreman Dhillon, Fengshen Kuo, Abraham Ari Hakimi, Philipp M Altrock, James J Mulé, Brandon J Manley |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Journal for ImmunoTherapy of Cancer. 11:e006195 |
| ISSN: |
2051-1426 |
| Popis: |
IntroductionIn clear cell renal cell carcinoma (ccRCC), tumor-associated macrophage (TAM) induction of CD8+T cells into a terminally exhausted state has been implicated as a major mechanism of immunotherapy resistance, but a deeper biological understanding is necessary.MethodsPrimary ccRCC tumor samples were obtained from 97 patients between 2004 and 2018. Multiplex immunofluorescence using lymphoid and myeloid markers was performed in seven regions of interest per patient across three predefined zones, and geospatial analysis was performed using Ripley’s K analysis, a methodology adapted from ecology.ResultsClustering of CD163+M2 like TAMs into the stromal compartment at the tumor–stroma interface was associated with worse clinical stage (tumor/CD163+nK(75): stage I/II: 4.4 (IQR −0.5 to 5.1); stage III: 1.4 (IQR −0.3 to 3.5); stage IV: 0.6 (IQR −2.1 to 2.1); p=0.04 between stage I/II and stage IV), and worse overall survival (OS) and cancer-specific survival (CSS) (tumor/CD163+nK(75): median OS–hi=149 months, lo=86 months, false-discovery rate (FDR)-adj. Cox pConclusionsGeospatial clustering of CD163+M2 like TAMs into the stromal compartment at the tumor–stromal interface was associated with poor clinical outcomes and CD8+T cell terminal exhaustion. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
