Purpose: Although a recent genomic landscape study identified molecular and genetic signatures of immune cytolytic activity (CYT) related to immune-mediated cancer elimination, less is known about the clinical relevance of CYT in the tumors linked to immune microenvironment in breast cancer. The aim of our study was to assess whether intratumor CYT associates with genetic alterations and tumor immune microenvironment, which impacts survival in breast cancer patients.
Experimental Design: We utilized genomic data from primary samples of 1,090 breast cancer patients with clinicopathologic information from The Cancer Genome Atlas (TCGA). We developed an immunogenomics pipeline that correlates CYT with clinical outcome and intratumor immune microenvironment, including infiltrating immune cell composition.
Results: Breast cancer displays a range of intratumor CYT. Patients with high CYT showed significantly better prognostic outcome, independent of age, hormonal status, and stage. CYT also has a strongly positive association with the expression of immune checkpoint genes such as PD1, PD-L1, and CTLA4, as well as regulatory T-cell (Treg) markers such as FOXP3 and CCR4. Enrichment of immune-response gene sets was observed in the high-CYT tumors. CYT was associated with higher composition of immune-elimination cells such as CD8+ T-cell, CD4+ T-cell, gamma delta T-cell, and M1 macrophage, as opposed to negatively associated with immunosuppressive cells, such as Treg and M2 macrophage. High CYT was also associated with improved survival in tumor-infiltrating lymphocyte (TIL)-positive breast cancer.
Conclusions: Patients with high CYT breast cancers show improved survival, likely due to high intratumor immunogenicity. CYT could also be used as a potential biomarker for immunologic response within tumors.
Citation Format: Tstutomu Kawaguchi, Qianya Qi, Xuan Peng, Kerry-Ann McDonald, Sumana Narayanan, Jessica Young, Song Liu, Li Yan, Kazuaki Takabe. Local immune cytolytic activity stratifies clinical outcome and is linked to the immune microenvironment in breast cancer [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 120.