• Chengming Liu, Sufei Zheng, Runsen Jin, Xinfeng Wang, Feng Wang, Ruochuan Zang, Haiyan Xu, Zhiliang Lu, Jianbing Huang, Yuanyuan Lei, Shuangshuang Mao, Yalong Wang, Xiaoli Feng, Nan Sun, Yan Wang, and Jie He.
• Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
• Cancer Lett. 2020 Feb 1; 470: 95-105.

AbstractImmune checkpoint inhibitors against PD-1/PD-L1 yield improved survival rates of KRAS-mutant NSCLC patients, who conferred a poor prognosis without effective targeted therapy until now. Yet, the underlying association between KRAS mutations and immune responses remains unclear. We performed an integrated analysis of the data from publicly available repositories and from clinical center cohorts to explore the association between KRAS mutation status and tumor immunity-associated features, including PD-L1 expression, CD8+ tumor-infiltrating lymphocytes (TILs) and tumor mutational burden (TMB). Our results revealed that KRAS mutations are correlated with an inflammatory tumor microenvironment and tumor immunogenicity, resulting in superior patient response to PD-1/PD-L1 inhibitors. Meanwhile, three-pool analysis further confirmed that KRAS-mutant NSCLC patients show remarkable clinical benefit from anti-PD-1/PD-L1 immunotherapy. In addition, a KRAS-mutant lung adenocarcinoma mouse model was established to estimate the relative efficacy of anti-PD-L1 monoclonal antibody monotherapy or combination treatment with docetaxel versus docetaxel alone. Most surprisingly, we found that PD-L1 blockade combined with docetaxel did not promote an anti-tumor response. These findings uncover that PD-1/PD-L1 blockade monotherapy may be the optimal therapeutic schedule in NSCLC patients harboring KRAS mutations.Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.

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