LAUSR

The tumor microenvironment is an important factor in cancer immunotherapy response. To further understand how a tumor affects the local immune system, we analyzed immune gene expression differences between matching normal and tumor tissues. We analyzed previously published and new gene expression data from solid cancers and isolated immune cell populations. We also determined the correlation between CD8, FoxP3 immunohistochemistry (IHC) and immune-related genes. Across solid TCGA cancers, we observed that regulatory T-cells (Tregs) were one of the main drivers of immune gene expression differences between normal and tumor tissues. A tumor-specific CD8 signature had slightly lower scores in tumor tissues compared to normal of most (12 of 16) cancers, while a Treg signature score was higher in tumor tissues of all cancers except liver. We clustered TCGA colorectal samples (626 patients) and a new separate testing data set (60 patients) into two groups according to Treg gene signature expression. The High Treg cluster had more colorectal tumors that were Consensus Molecular Subtype 1/4, right-sided and microsatellite-instable, compared to the Low Treg cluster. Finally, we determined the correlation between CD8, FoxP3 immunohistochemistry (IHC) and our gene signatures and found that in this small data set correlation between signature and IHC overall was low, but samples in the High Treg cluster had significantly more CD8+ and FoxP3+ cells compared to the Low Treg cluster. We conclude that high Treg signature expression scores correlate with high overall immune gene expression. Using this novel way of classifying patients, more colorectal tumors with high immune activation were identified compared to other colorectal subtyping methods. Further research will reveal if this Treg-based subtyping improves the identification of patients that may benefit from cancer immunotherapy. Citation Format: Jurriaan Brouwer, Wei-Yi Cheng, Anna Bauer-Mehren, Daniela Maisel, Katharina Lechner, Emilia Andersson, Joel T. Dudley, Francesca Milletti. Regulatory T-cell genes drive altered immune microenvironment in adult solid cancers and allow for immune contextual patient subtyping [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1027.