Comprehensive assessment of immune context and immunotherapy response via noninvasive imaging in gastric cancer

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Abstract

BACKGROUND The tumor immune microenvironment can provide prognostic and therapeutic information. We aimed to develop noninvasive imaging biomarkers from computed tomography (CT) for comprehensive evaluation of immune context and investigate their associations with prognosis and immunotherapy response in gastric cancer (GC).METHODS This study involved 2,600 patients with GC from 9 independent cohorts. We developed and validated 2 CT imaging biomarkers (lymphoid radiomics score [LRS] and myeloid radiomics score [MRS]) for evaluating the IHC-derived lymphoid and myeloid immune context respectively, and integrated them into a combined imaging biomarker [LRS/MRS: low(−) or high(+)] with 4 radiomics immune subtypes: 1 (−/−), 2 (+/−), 3 (−/+), and 4 (+/+). We further evaluated the imaging biomarkers’ predictive values on prognosis and immunotherapy response.RESULTS The developed imaging biomarkers (LRS and MRS) had a high accuracy in predicting lymphoid (AUC range: 0.765–0.773) and myeloid (AUC range: 0.736–0.750) immune context. Further, similar to the IHC-derived immune context, 2 imaging biomarkers (HR range: 0.240–0.761 for LRS; 1.301–4.012 for MRS) and the combined biomarker were independent predictors for disease-free and overall survival in the training and all validation cohorts (all P < 0.05). Additionally, patients with high LRS or low MRS may benefit more from immunotherapy (P < 0.001). Further, a highly heterogeneous outcome on objective response ​rate was observed in 4 imaging subtypes: 1 (−/−) with 27.3%, 2 (+/−) with 53.3%, 3 (−/+) with 10.2%, and 4 (+/+) with 30.0% (P < 0.0001).CONCLUSION The noninvasive imaging biomarkers could accurately evaluate the immune context and provide information regarding prognosis and immunotherapy for GC.

Authors

Zepang Sun, Taojun Zhang, M. Usman Ahmad, Zixia Zhou, Liang Qiu, Kangneng Zhou, Wenjun Xiong, Jingjing Xie, Zhicheng Zhang, Chuanli Chen, Qingyu Yuan, Yan Chen, Wanying Feng, Yikai Xu, Lequan Yu, Wei Wang, Jiang Yu, Guoxin Li, Yuming Jiang