Research Paper Volume 11, Issue 23 pp 11576—11590
Robust immunoscore model to predict the response to anti-PD1 therapy in melanoma
- 1 Department of Gastric Surgery and Melanoma Surgical Section, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- 2 Department of Hematologic Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- 3 VIP Department, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- 4 Department of Gastric Surgery, The 6th Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- 5 Department of Experimental Research (Cancer Institute), Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Received: September 24, 2019 Accepted: November 20, 2019 Published: December 3, 2019
https://doi.org/10.18632/aging.102556How to Cite
Copyright © 2019 Nie et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.