Eckstein, Markus and Strissel, Pamela and Strick, Reiner and Weyerer, Veronika and Wirtz, Ralph and Pfannstiel, Carolin and Wullweber, Adrian and Lange, Fabienne and Erben, Philipp and Stoehr, Robert and Bertz, Simone and Geppert, Carol Imanuel and Fuhrich, Nicole and Taubert, Helge and Wach, Sven and Breyer, Johannes and Otto, Wolfgang and Burger, Maximilian and Bolenz, Christian and Keck, Bastian and Wullich, Bernd and Hartmann, Arndt and Sikic, Danijel (2020) Cytotoxic T-cell-related gene expression signature predicts improved survival in muscle-invasive urothelial bladder cancer patients after radical cystectomy and adjuvant chemotherapy. JOURNAL FOR IMMUNOTHERAPY OF CANCER, 8 (1): e000162. ISSN , 2051-1426
Full text not available from this repository. (Request a copy)Abstract
Background Assessment of the immune status of muscle-invasive bladder cancer (MIBC) has previously shown to be prognostically relevant after treatment with curative intent. We conducted this study to develop a clinically applicable immune gene expression assay to predict prognosis and adjuvant chemotherapy benefit. Patients and methods Gene expression of CD3Z, CD8A and CXCL9, immune cell (IC) populations including stromal tumor infiltrating lymphocytes (sTILs), T-cells, natural killer cells (NK-cells), macrophages, Programmed cell death protein 1 positive (PD-1) IC and tumor subtypes (MD Anderson Cancer Center/MDACC-approach) were assessed in 187 MIBC patients (Comprehensive Cancer Center Erlangen-EMN/CCC-EMN-cohort). A gene expression signature was derived by hierarchical-clustering and validated in The Cancer Genome Atlas (TCGA)-cohort. IC populations in the TCGA cohort were assessed via CIBERSORT. Benefit of platinum-containing adjuvant chemotherapy was assessed in a pooled cohort of 125 patients. Outcome measurements were disease specific survival, disease-free survival and overall survival. Results The gene expression signature of CXCL9, CD3Z and CD8A correlates with quantitative amounts of specific IC populations and sTILs (CCC-EMN: rho -range: 0.44-0.74; TCGA: rho -range: 0.56-0.82) and allows stratification of three different inflammation levels (inflamed high, inflamed low, uninflamed). Highly inflamed tumors are preferentially basal subtype and show favorable 5-year survival rates of 67.3% (HR=0.27; CCC-EMN) and 55% (HR=0.41; TCGA). Uninflamed tumors are predominantly luminal subtypes and show low 5-year survival rates of 28% (CCC-EMN) and 36% (TCGA). Inflamed tumors exhibit higher levels of PD-1 and Programmed cell death 1 ligand 1 (PD-L1). Patients undergoing adjuvant platinum-based chemotherapy with 'inflamed high' tumors showed a favorable 5-year survival rate of 64% (HR=0.27; merged CCC-EMN and TCGA cohort). Conclusion The gene expression signature of CD3Z, CD8A and CXCL9 can assess the immune status of MIBC and stratify the survival of MIBC patients undergoing surgery and adjuvant platinum-based chemotherapy. Furthermore, the assay can identify patients with immunological hot tumors with particular high expression of PD-L1 potentially suitable for immunotherapy.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TUMOR-INFILTRATING LYMPHOCYTES; CARCINOMA; ATEZOLIZUMAB; THERAPY; IDENTIFICATION; MULTICENTER; GUIDELINES; SUBTYPES; PD-L1; BASAL; immunology; pathology; urology |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Urologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 06 Apr 2021 09:13 |
| Last Modified: | 06 Apr 2021 09:13 |
| URI: | https://pred.uni-regensburg.de/id/eprint/45406 |
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