Ming Yi1, Anping Li2, Linghui Zhou3, Qian Chu2, Suxia Luo4, Kongming Wu5,6. 1. Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. 2. Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, 450008, China. 3. Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, 310003, China. 4. Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, 450008, China. luosxrm@163.com. 5. Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. kmwu@tjh.tjmu.edu.cn. 6. Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, 450008, China. kmwu@tjh.tjmu.edu.cn.
Abstract
BACKGROUND: Lung adenocarcinoma (LUAD) is a common pulmonary malignant disease with a poor prognosis. There were limited studies investigating the influences of the tumor immune microenvironment on LUAD patients' survival and response to immune checkpoint inhibitors (ICIs). METHODS: Based on TCGA-LUAD dataset, we constructed a prognostic immune signature and validated its predictive capability in the internal as well as total datasets. Then, we explored the differences of tumor-infiltrating lymphocytes, tumor mutation burden, and patients' response to ICI treatment between the high-risk score group and low-risk score group. RESULTS: This immune signature consisted of 17 immune-related genes, which was an independent prognostic factor for LUAD patients. In the low-risk score group, patients had better overall survival. Although the differences were non-significant, patients with low-risk scores had more tumor-infiltrating follicular helper T cells and fewer macrophages (M0), which were closely related to clinical outcomes. Additionally, the total TMB was markedly decreased in the low-risk score group. Using immunophenoscore as a surrogate of ICI response, we found that patients with low-risk scores had significantly higher immunophenoscore. CONCLUSION: The 17-immune-related genes signature may have prognostic and predictive relevance with ICI therapy but needs prospective validation.
BACKGROUND:Lung adenocarcinoma (LUAD) is a common pulmonary malignant disease with a poor prognosis. There were limited studies investigating the influences of the tumor immune microenvironment on LUAD patients' survival and response to immune checkpoint inhibitors (ICIs). METHODS: Based on TCGA-LUAD dataset, we constructed a prognostic immune signature and validated its predictive capability in the internal as well as total datasets. Then, we explored the differences of tumor-infiltrating lymphocytes, tumor mutation burden, and patients' response to ICI treatment between the high-risk score group and low-risk score group. RESULTS: This immune signature consisted of 17 immune-related genes, which was an independent prognostic factor for LUAD patients. In the low-risk score group, patients had better overall survival. Although the differences were non-significant, patients with low-risk scores had more tumor-infiltrating follicular helper T cells and fewer macrophages (M0), which were closely related to clinical outcomes. Additionally, the total TMB was markedly decreased in the low-risk score group. Using immunophenoscore as a surrogate of ICI response, we found that patients with low-risk scores had significantly higher immunophenoscore. CONCLUSION: The 17-immune-related genes signature may have prognostic and predictive relevance with ICI therapy but needs prospective validation.
Authors: Patrick M Forde; Jamie E Chaft; Kellie N Smith; Valsamo Anagnostou; Tricia R Cottrell; Matthew D Hellmann; Marianna Zahurak; Stephen C Yang; David R Jones; Stephen Broderick; Richard J Battafarano; Moises J Velez; Natasha Rekhtman; Zachary Olah; Jarushka Naidoo; Kristen A Marrone; Franco Verde; Haidan Guo; Jiajia Zhang; Justina X Caushi; Hok Yee Chan; John-William Sidhom; Robert B Scharpf; James White; Edward Gabrielson; Hao Wang; Gary L Rosner; Valerie Rusch; Jedd D Wolchok; Taha Merghoub; Janis M Taube; Victor E Velculescu; Suzanne L Topalian; Julie R Brahmer; Drew M Pardoll Journal: N Engl J Med Date: 2018-04-16 Impact factor: 91.245