Cytotoxic Lymphocyte-Related Gene Signature in Triple-Negative Breast Cancer

To curate the signature genes of cytotoxic lymphocytes (CLs) and explore the heterogeneity based on the CL-related (CLR) gene signature, we analyzed the gene expression of 592 patients with histologically diagnosed triple-negative breast cancer. Based on the 13-gene panel, CLR signatures were curated and associated with the stage of tumor size. Patients in the CLR-low group exhibited the worse overall survival (OS) (median OS, 75.23 months vs. 292.66 months, p < 0.0001) and were characterized by the upregulation of the NF-kappa B, Wnt, and p53 pathways, the positive regulation of angiogenesis, and a higher expression of immune checkpoints including CTLA4, LAG3, CD86, ICOS, ICOSLG, and TNFSF9. In cancer immunotherapy cohorts (GSE157284, GSE35640, IMvigor210), a higher CLR signature score was remarkably associated with greater tumor shrinkage and immune characteristics consisting of higher PD-L1 and neoantigen expression, as well as an inflamed tumor microenvironment. In the pan-cancer atlas, the CLR signature was notably associated with patient survival and revealed a profound heterogeneity across the malignancy types. In sum, the CLR signature is a promising indicator for immune characteristics, tumor shrinkage, and survival outcomes following cancer immunotherapy in addition to the prognostic heterogeneity in the pan-cancer atlas.

Automated summary

By analyzing the gene expression of 592 patients with triple-negative breast cancer, researchers were able to curate a gene signature for cytotoxic lymphocytes (CLs) and explore the heterogeneity based on this CL-related (CLR) gene signature. The CLR signature was associated with tumor size and patients in the CLR-low group had worse overall survival. In addition, the CLR signature was also associated with immune characteristics, tumor shrinkage, and survival outcomes following cancer immunotherapy, as well as prognostic heterogeneity across different malignancies.