Spatial multi-omics revealed the impact of tumor ecosystem heterogeneity on immunotherapy efficacy in patients with advanced non-small cell lung cancer treated with bispecific antibody.
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IF: 12.469
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Cited by: 4
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Abstract

Immunotherapy for malignant tumors has made great progress, but many patients do not benefit from it. The complex intratumoral heterogeneity (ITH) hindered the in-depth exploration of immunotherapy. Conventional bulk sequencing has masked intratumor complexity, preventing a more detailed discovery of the impact of ITH on treatment efficacy. Hence, we initiated this study to explore ITH at the multi-omics spatial level and to seek prognostic biomarkers of immunotherapy efficacy considering the presence of ITH. Using the segmentation strategy of digital spatial profiling (DSP), we obtained differential information on tumor and stromal regions at the proteomic and transcriptomic levels. Based on the consideration of ITH, signatures constructed by candidate proteins in different regions were used to predict the efficacy of immunotherapy. Eighteen patients treated with a bispecific antibody (bsAb)-KN046 were enrolled in this study. The tumor and stromal areas of the same samples exhibited distinct features. Signatures consisting of 11 and 18 differentially expressed DSP markers from the tumor and stromal areas, respectively, were associated with treatment response. Furthermore, the spatially resolved signature identified from the stromal areas showed greater predictive power for bsAb immunotherapy response (area under the curve=0.838). Subsequently, our stromal signature was validated in an independent cohort of patients with non-small cell lung cancer undergoing immunotherapy. We deciphered ITH at the spatial level and demonstrated for the first time that genetic information in the stromal region can better predict the efficacy of bsAb treatment. NCT03838848.

Keywords

Omics
SM-Omics
biomarkers, tumor
immunotherapy
lung neoplasms

MeSH terms

Humans
Antibodies, Bispecific
Carcinoma, Non-Small-Cell Lung
Ecosystem
Immunotherapy
Lung Neoplasms
Multiomics
Proteomics

Authors

Song, Xinyu
Xiong, Anwen
Wu, Fengying
Li, Xuefei
Wang, Jing
Jiang, Tao
Chen, Peixin
Zhang, Xiaoshen
Zhao, Zhikai
Liu, Huifang
Cheng, Lei
Zhao, Chao
Wang, Zhehai
Pan, Chaohu
Cui, Xiaoli
Xu, Ting
Luo, Haitao
Zhou, Caicun