Abstract |
This study aimed to construct immune-related predictors to identify responders to anti-PD1 therapy of melanoma through CIBERSORT algorithm. Using the least absolute shrinkage and selection operator (LASSO) logistic regression, we constructed an immunoscore consisting of 8 immune subsets to predict the anti-PD1 response. This score achieved an overall accuracy of AUC = 0.77, 0.80 and 0.73 in the training cohort, validation cohort and on-anti-PD1 cohort, respectively. Patients with high immunoscores had significantly higher objective response rates (ORRs) than did those with low immunoscores (ORR: 53.8% vs 17.7%, P < 0.001 for entire pre-anti-PD1 cohort; 42.1% vs 15.1%, P = 0.022 for on-anti-PD1 cohort; 66.7% vs 16.7%, P = 0.038 for neoadjuvant anti-PD1 cohort). Prolonged survival trends were observed in high-immunoscore group (1-year PFS: 42.4% vs 14.3%, P = 0.059; 3-year OS: 41.5% vs 31.6%, P = 0.057). Furthermore, we found that high-immunoscore group exhibited higher fractions of tumor-infiltrating lymphocytes and an increased IFN-γ response. Analysis of the results of the GSEA indicated a significant enrichment of antitumor immunity pathways in the high-immunoscore group. Therefore, this study indicated that we constructed a robust immunoscore model to predict the anti-PD1 response of metastatic melanoma and the neoadjuvant anti-PD1 response of resectable melanoma.
|
Authors | Run-Cong Nie, Shu-Qiang Yuan, Yun Wang, Ying-Bo Chen, Yan-Yu Cai, Shi Chen, Shu-Man Li, Jie Zhou, Guo-Ming Chen, Tian-Qi Luo, Zhi-Wei Zhou, Yuan-Fang Li |
Journal | Aging
(Aging (Albany NY))
Vol. 11
Issue 23
Pg. 11576-11590
(12 03 2019)
ISSN: 1945-4589 [Electronic] United States |
PMID | 31796647
(Publication Type: Journal Article)
|
Chemical References |
- Antineoplastic Agents
- PDCD1 protein, human
- Programmed Cell Death 1 Receptor
|
Topics |
- Adult
- Aged
- Aged, 80 and over
- Antineoplastic Agents
(pharmacology, therapeutic use)
- Databases, Genetic
- Female
- Gene Expression Regulation, Neoplastic
(drug effects, immunology)
- Humans
- Logistic Models
- Male
- Melanoma
(drug therapy)
- Middle Aged
- Programmed Cell Death 1 Receptor
(antagonists & inhibitors)
|