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| Content Provider | frontiers |
|---|---|
| Author | Su, Xiaofan Jin, Haoxuan Du, Ning Wang, Jiaqian Lu, Huiping Xiao, Jinyuan Li, Xiaoting Yi, Jian Gu, Tiantian Dan, Xu Gao, Zhibo Li, Manxiang |
| Abstract | Background: Immune checkpoint inhibitors (ICIs) induce durable responses, but only a minority of patients achieve clinical benefits. The development of gene expression profiling of tumor transcriptomes has enabled identifying prognostic gene expression signatures and patient selection with targeted therapies. Methods: Immune exclusion score (IES) was built by elastic net-penalized Cox proportional hazards (PHs) model in the discovery cohort and validated via four independent cohorts. The survival differences between the two groups were compared using Kaplan-Meier analysis. Both GO and KEGG analyses were performed for functional annotation. CIBERSORTx was also performed to estimate the relative proportion of immune-cell types. Results: A fifteen-genes immune exclusion score (IES) was developed in the discovery cohort of 65 patients treated with anti-PD-(L)1 therapy. The ROC efficiencies of 1- and 3- year prognosis were 0.842 and 0.82, respectively. Patients with low IES showed a longer PFS (p=0.003) and better response rate (ORR: 43.8% vs 18.2%, p=0.03). We found that patients with low IES enriched with high expression of immune eliminated cell genes, such as CD8+ T cells, CD4+ T cells, NK cells and B cells. IES was positively correlated with other immune exclusion signatures. Furthermore, IES was successfully validated in four independent cohorts (Riaz’s SKCM, Liu’s SKCM, Nathanson’s SKCM and Braun’s ccRCC, n = 367). IES was also negatively correlated with T cell–inflamed signature and independent of TMB. Conclusions: This novel IES model encompassing immune-related biomarkers might serve as a promising tool for the prognostic prediction of immunotherapy. |
| ISSN | 2234943X |
| DOI | 10.3389/fonc.2022.930589 |
| Volume Number | 12 |
| Journal | Frontiers in Oncology |
| Language | English |
| Publisher Date | 2022-06-27 |
| Access Restriction | Open |
| Subject Keyword | Gene expression profile Response Checkpoint inhibitors Biomarker Immune exclusion Prognosis |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cancer Research Oncology |
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