Abstract 1079: Prognostic role of tumor microenvironment in correlation with CD8+ T cells in TCGA pan-cancer
Authors: Yoo Shin Hye , Park Changhee , Ock Chan-Young , Kim Miso , Keam Bhumsuk , Kim Tae Min , Kim Dong-Wan , Heo Dae Seog 
Published: August 2019

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 CD8low, CD8high-Xlow/int, and CD8high-Xhigh 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 naïve 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 CD8high-Treghigh group than in CD8high-Treglow/int group (P=0.0476). The fraction of CD8high-Treghigh 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.