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An Empirical Approach Leveraging Tumorgrafts to Dissect the Tumor Microenvironment in Renal Cell Carcinoma Identifies Missing Link to Prognostic Inflammatory Factors

We undertook an empirical approach to dissect the tumor microenvironment by developing a bulk tumor dissection algorithm, DisHet, and leveraging RNA-Seq data of tumorgrafts (patient-derived tumors implanted in mice), in which only the tumor cell component expands. We found that approximately 65% of previously defined immune signature genes are not abundantly expressed in the Renal Cell Carcinoma (RCC) microenvironment, and we identified more than two times as many novel immune/stromal transcripts. By using refined immune/stroma-specific genes and genomics, electronic medical record data and imaging data of 1084 RCC patients, we discovered a highly-inflamed pan-RCC subtype enriched for Treg cells, NK cells, Th1 cells, neutrophils, macrophages, B cells, and CD8+ T cells. This inflamed subtype (IS) is enriched for aggressive RCCs, including BAP1-deficient clear-cell and type 2 papillary tumors. Interestingly, IS is correlated with systemic manifestations of inflammation in patients such as thrombocytosis and anemia, whose pathogenesis were poorly defined and have been predictors of poor prognosis in RCC. Indeed, we discovered that IS is a strong predictor of poor survival. Lastly, our analyses show that tumor cells may drive stromal immune response. Overall, these data provide a missing link between the tumor cells, the tumor microenvironment, and systemic factors.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001003895 Illumina HiSeq 2000 59
Publications Citations
An Empirical Approach Leveraging Tumorgrafts to Dissect the Tumor Microenvironment in Renal Cell Carcinoma Identifies Missing Link to Prognostic Inflammatory Factors.
Cancer Discov 8: 2018 1142-1155
88
Complement as Prognostic Biomarker and Potential Therapeutic Target in Renal Cell Carcinoma.
J Immunol 205: 2020 3218-3229
10
Multi-tumor analysis of cancer-stroma interactomes of patient-derived xenografts unveils the unique homeostatic process in renal cell carcinomas.
iScience 24: 2021 103322
3