Predicting which patients will progress to metastatic disease after surgery for non-metastatic clear cell renal cell carcinoma (ccRCC) is difficult; however, recent data suggest that tumor immune cell infiltration could be used as a biomarker. We evaluated the quantity and type of immune cells infiltrating ccRCC tumors for associations with metastatic progression following attempted curative surgery. We quantified immune cell densities in the tumor microenvironment and validated our findings in two independent patient cohorts with multi-region sampling to investigate the impact of heterogeneity on prognostic accuracy. For non-metastatic ccRCC, increased CD8+ T cell infiltration was associated with a reduced likelihood of progression to metastatic disease. Interestingly, patients who progressed to metastatic disease also had increased percentages of exhausted CD8+ T cells. Finally, we evaluated the spatial heterogeneity of the immune infiltration and demonstrated that patients without metastatic progression had CD8+ T cells in closer proximity to ccRCC cells. These data strengthen the evidence for CD8+ T cell infiltration as a prognostic biomarker in non-metastatic ccRCC and demonstrate that multi-region sampling may be necessary to fully characterize immune infiltration within heterogeneous tumors. Tumor CD8+ T cell infiltration should be investigated as a biomarker in adjuvant systemic therapy clinical trials for high-risk non-metastatic RCC.
Cancers. 2024 Jan 23*** epublish ***
Daniel D Shapiro, Taja Lozar, Lingxin Cheng, Elliot Xie, Israa Laklouk, Moon Hee Lee, Wei Huang, David F Jarrard, Glenn O Allen, Rong Hu, Toshi Kinoshita, Karla Esbona, Paul F Lambert, Christian M Capitini, Christina Kendziorski, Edwin Jason Abel
Department of Urology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA., McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI 53706, USA., Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA., Department of Pathology, University of California, Los Angeles, Los Angeles, CA 90024, USA., Department of Pathology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA., Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.