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A 12-chemokine gene signature is associated with the enhanced immunogram scores and is relevant for precision immunotherapy

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Abstract

Advances in the understanding of checkpoint blockade immunotherapy have suggested that boosting the cancer-immunity cycle (CIC) can help induce regression of tumors. However, good efficacy only occurs in a subset of patients. Predictive biomarkers that can reflect the tumor microenvironment (TME) and CIC may have great potential. More recently, the presence of intratumoral tertiary lymphoid structures (TLSs) has also been correlated with clinical benefit in patients. In this study, we comprehensively measured the immunogram scores (IGSs) for the CIC and explored the associations between immunological and mutational features and a 12-chemokine metagene TLS signature in data from The Cancer Genome Atlas (TCGA). Three immunotherapy datasets were further applied for validation. In the TCGA dataset, we observed that the 12-chemokine TLS signature score was positively associated with the enhanced IGSs as represented by increased tumor mutational burden (TMB) and neoantigen burden (TNB), enriched immune cell (IC) infiltration, and elevated cytolytic activity and checkpoint expression. Specifically, in bladder cancer and melanoma, the high 12-chemokine TLS signature score was found to potentially reflect an expanded cancer-immunity status characterized by high TNB and an immune-inflamed feature. The predictive and prognostic value of the 12-chemokine TLS signature was further validated in several immunotherapy datasets. The score of the 12-chemokine TLS signature may serve as a pancancer marker of the immune-active phenotype. The 12-chemokine TLS signature showed promise as a predictive and prognostic biomarker for ICB efficacy, especially in melanoma and bladder cancer.

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Data availability

All data analyzed in our study were obtained from publicly available, online datasets. The raw data of this study are derived from the TCGA database and GEO data portal, as mentioned in the Materials and Methods.

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Not applicable.

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Acknowledgements

We thank the professional English-speaking editors at American Journal Experts for assistance with improving the quality of the language.

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Authors and Affiliations

  1. Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China

    Xingchen Li, Xiu Liu, Kai Ou & Lin Yang

  2. Genecast Biotechnology Co., Ltd., 88 Danshan Road, Xidong Chuangrong Building, Suite D-401, Xishan District, Wuxi, 214104, Jiangsu, China

    Zhiyi Wan

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  1. Xingchen Li
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Contributions

XL, LY: Conceptualization. ZW: Acquisition of the data. XL, XL: Formal analysis and investigation. XL: Drafting of the manuscript. KO, ZW: Statistical analysis. LY: Supervision. All authors: Critical revision of the manuscript for important intellectual content.

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Correspondence to Lin Yang.

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Li, X., Wan, Z., Liu, X. et al. A 12-chemokine gene signature is associated with the enhanced immunogram scores and is relevant for precision immunotherapy. Med Oncol 39, 43 (2022). https://doi.org/10.1007/s12032-021-01635-2

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  • DOI: https://doi.org/10.1007/s12032-021-01635-2

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