Frontiers in Immunology (Apr 2021)
From the Immune Profile to the Immunoscore: Signatures for Improving Postsurgical Prognostic Prediction of Pancreatic Neuroendocrine Tumors
- Miaoyan Wei,
- Miaoyan Wei,
- Miaoyan Wei,
- Miaoyan Wei,
- Miaoyan Wei,
- Jin Xu,
- Jin Xu,
- Jin Xu,
- Jin Xu,
- Jin Xu,
- Jie Hua,
- Jie Hua,
- Jie Hua,
- Jie Hua,
- Jie Hua,
- Qingcai Meng,
- Qingcai Meng,
- Qingcai Meng,
- Qingcai Meng,
- Qingcai Meng,
- Chen Liang,
- Chen Liang,
- Chen Liang,
- Chen Liang,
- Chen Liang,
- Jiang Liu,
- Jiang Liu,
- Jiang Liu,
- Jiang Liu,
- Jiang Liu,
- Bo Zhang,
- Bo Zhang,
- Bo Zhang,
- Bo Zhang,
- Bo Zhang,
- Wei Wang,
- Wei Wang,
- Wei Wang,
- Wei Wang,
- Wei Wang,
- Xianjun Yu,
- Xianjun Yu,
- Xianjun Yu,
- Xianjun Yu,
- Xianjun Yu,
- Si Shi,
- Si Shi,
- Si Shi,
- Si Shi,
- Si Shi
Affiliations
- Miaoyan Wei
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Miaoyan Wei
- Pancreatic Cancer Multidisciplinary Center, Fudan University Shanghai Cancer Center, Shanghai, China
- Miaoyan Wei
- Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China
- Miaoyan Wei
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
- Miaoyan Wei
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Jin Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Jin Xu
- Pancreatic Cancer Multidisciplinary Center, Fudan University Shanghai Cancer Center, Shanghai, China
- Jin Xu
- Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China
- Jin Xu
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
- Jin Xu
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Jie Hua
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Jie Hua
- Pancreatic Cancer Multidisciplinary Center, Fudan University Shanghai Cancer Center, Shanghai, China
- Jie Hua
- Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China
- Jie Hua
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
- Jie Hua
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Qingcai Meng
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Qingcai Meng
- Pancreatic Cancer Multidisciplinary Center, Fudan University Shanghai Cancer Center, Shanghai, China
- Qingcai Meng
- Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China
- Qingcai Meng
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
- Qingcai Meng
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Chen Liang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Chen Liang
- Pancreatic Cancer Multidisciplinary Center, Fudan University Shanghai Cancer Center, Shanghai, China
- Chen Liang
- Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China
- Chen Liang
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
- Chen Liang
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Jiang Liu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Jiang Liu
- Pancreatic Cancer Multidisciplinary Center, Fudan University Shanghai Cancer Center, Shanghai, China
- Jiang Liu
- Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China
- Jiang Liu
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
- Jiang Liu
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Bo Zhang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Bo Zhang
- Pancreatic Cancer Multidisciplinary Center, Fudan University Shanghai Cancer Center, Shanghai, China
- Bo Zhang
- Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China
- Bo Zhang
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
- Bo Zhang
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Wei Wang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Wei Wang
- Pancreatic Cancer Multidisciplinary Center, Fudan University Shanghai Cancer Center, Shanghai, China
- Wei Wang
- Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China
- Wei Wang
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
- Wei Wang
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Xianjun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Xianjun Yu
- Pancreatic Cancer Multidisciplinary Center, Fudan University Shanghai Cancer Center, Shanghai, China
- Xianjun Yu
- Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China
- Xianjun Yu
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
- Xianjun Yu
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Si Shi
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Si Shi
- Pancreatic Cancer Multidisciplinary Center, Fudan University Shanghai Cancer Center, Shanghai, China
- Si Shi
- Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China
- Si Shi
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
- Si Shi
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- DOI
- https://doi.org/10.3389/fimmu.2021.654660
- Journal volume & issue
-
Vol. 12
Abstract
ObjectiveImmune infiltration plays an important role in tumor development and progression and shows promising prognostic value in numerous tumors. In this study, we aimed to identify the role of immune infiltration in pancreatic neuroendocrine tumors (Pan-NETs) and to establish an Immunoscore system to improve the prediction of postsurgical recurrence-free survival.MethodsTo derive transcriptional signatures and deconvolute specific immune populations, two GEO datasets containing 158 Pan-NET patients were reanalyzed to summarize the immune infiltration landscape and identify immune-related signatures. Using real-time reverse transcription-polymerase chain reaction, immunofluorescence and immunochemistry methods, candidate signatures were further detected. The least absolute shrinkage and selection operator (LASSO) logistic regression model used statistically significant survival predicators in the training cohort (n=125) to build an Immunoscore system. The prognostic and predictive accuracy was validated in an external independent cohort of 77 patients.ResultsThe immune infiltration profile in Pan-NETs showed significant heterogeneity, among which accumulated immune cells, T lymphocytes and macrophages were predominant. Fourteen statistically significant immune-related signatures were further identified in the screening cohort. The Immunoscore system for Pan-NETs (ISpnet) consisting of six immune features (CCL19, IL-16, CD163, IRF4, CD8PT and CD8IT) was constructed to classify patients as high and low risk in the training cohort (cutoff value = 2.14). Low-risk patients demonstrated longer 5-year recurrence-free survival (HR, 0.061; 95% CI, 0.026 to 0.14; p < 0.0001), with fewer recurrences and better prognoses. To predict the individual risk of recurrence, a nomogram incorporating both immune signatures and clinicopathological characteristics was developed.ConclusionOur model, ISpnet, captures immune feature-associated prognostic indicators in Pan-NETs and represents the first immune feature-based score for the postsurgical prognostic prediction. The nomogram based on the ISpnet and independent clinical risk factors might facilitate decision-making regarding early recurrence risk monitoring, identify high-risk patients in need of adjuvant therapy, and provide auxiliary guidance for patients with Pan-NETs that may benefit from immunotherapy in clinical trials.
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