IFN-α/β/IFN-γ/IL-15 pathways identify GBP1-expressing tumors with an immune-responsive phenotype
Lei Wang, Yuxuan Wei, Zheng Jin, Fangfang Liu, Xuchang Li, Xiaoli Zhang, Xiumei Bai, Qingzhu Jia, Bo Zhu, Qian Chu
Abstract
Abstract Immunotherapy is widely used in cancer treatment; however, only a subset of patients responds well to it. Significant efforts have been made to identify patients who will benefit from immunotherapy. Successful anti-tumor immunity depends on an intact cancer-immunity cycle, especially long-lasting CD8 + T-cell responses. Interferon (IFN)-α/β/IFN-γ/interleukin (IL)-15 pathways have been reported to be involved in the development of CD8 + T cells. And these pathways may predict responses to immunotherapy. Herein, we aimed to analyze multiple public databases to investigate whether IFN-α/β/IFN-γ/IL-15 pathways could be used to predict the response to immunotherapy. Results showed that IFN-α/β/IFN-γ/IL-15 pathways could efficiently predict immunotherapy response, and guanylate-binding protein 1 ( GBP1 ) could represent the IFN-α/β/IFN-γ/IL-15 pathways. In public and private cohorts, we further demonstrated that GBP1 could efficiently predict the response to immunotherapy. Functionally, GBP1 was mainly expressed in macrophages and strongly correlated with chemokines involved in T-cell migration. Therefore, our study comprehensively investigated the potential role of GBP1 in immunotherapy, which could serve as a novel biomarker for immunotherapy and a target for drug development.