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• W2955963262 abstract "Purpose : Tumor microenvironment (TME) is a complex mixture of cells around tumor, showing different associations with tumor growth and survival outcomes. CD8 + T cell plays a key role in adaptive anti-tumor immunity and can predict favorable prognosis with better outcome from immunotherapy. However, little has been known whether various components of TME in correlation with CD8 + T cells affect prognosis. We aimed to investigate the prognostic role of immune cells in TME in correlation with CD8 + T cells using The Cancer Genome Atlas (TCGA) pan-cancer database. Experimental Design : The fraction of 21 immune cell subpopulations in TME and CD8 + T cell were extracted from mRNA expression data obtained by RNA sequencing of the TCGA samples to which a deconvolution algorithm (CIBERSORT) was applied. The samples were classified into CD8 low , CD8 high -X low/int , and CD8 high -X high groups (X is a component of TME), and survival was compared between them in TCGA pan-cancer and each cancer cohort. To determine the associations between each cell type and treatment outcomes, we also evaluated the immune cell subpopulations with CD8 + T cell in patients treated with programmed death-1 blockades using previously reported data on the nCounter system by the PanCancer 730-Immune Panel (GEO accession number: GSE93157). Results : Profiles of immune subpopulation in correlation with CD8 + T cell varied between different cancer types. In TCGA pan-cancer cohort with available survival data ( N =8903), increased regulatory T cells (Treg) ( P =2.48× 10 -4 ), M1 and M2 macrophages ( P =9.53× 10 -3 ; P =4.72× 10 -6 , respectively), resting natural killer cells ( P =7.29× 10 -4 ), and activated dendritic cells ( P =0.00579) were associated with poor prognosis despite high level of CD8 + T cells, whereas elevated germinal center follicular helper T cells ( P =8.44 × 10 -5 ) and naive B cell ( P =2.46× 10 -7 ) were good prognostic subpopulations. By each cancer type, kidney cancers (renal papillary tumors and clear cell carcinoma) showed significantly poor prognostic role of Treg (Hazard ratio (HR) 2.59, 95% confidence interval (CI) 1.13 to 5.93; HR 1.62, 95% CI 1.07 to 2.45, respectively). In patients treated with immunotherapy ( N =65), shorter progression-free survival was observed in CD8 high -Treg high group than in CD8 high -Treg low/int group ( P =0.0476). The fraction of CD8 high -Treg high group was higher in non-responders than in responders (15.6% vs. 5.0%). Conclusions : Our findings suggest that differences in immune cell subpopulations even with high CD8 + T cell might determine the prognosis. Immunosuppressive components in TME such as Treg can be negative factor for both prognosis and response to immunotherapy. A large prospective study is needed to validate the negative predictive role of immunosuppressive TME for patients treated with immunotherapy. Citation Format: Shin Hye Yoo, Changhee Park, Chan-Young Ock, Miso Kim, Bhumsuk Keam, Tae Min Kim, Dong-Wan Kim, Dae Seog Heo. Prognostic role of tumor microenvironment in correlation with CD8 + T cells in TCGA pan-cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1079." @default.
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• W2955963262 date "2019-07-01" @default.
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• W2955963262 title "Abstract 1079: Prognostic role of tumor microenvironment in correlation with CD8+T cells in TCGA pan-cancer" @default.
• W2955963262 doi "https://doi.org/10.1158/1538-7445.sabcs18-1079" @default.
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