Abstract
ObjectiveTumor-infiltrating immune cells might add a predictive value for the prognostic stratification of patients with pancreatic ductal adenocarcinoma (PDAC) and chemotherapy response. We aimed to develop a prognostic model based on the tumor-infiltrating immune cell signature to improve the prediction of survival and chemotherapy benefits of patients with PDAC.MethodsThe abundance of tumor-infiltrating immune cells for 661 patients with PDAC from four different cohorts with survival data was collected in the training cohorts. Cox regression analysis and meta-analysis of immune cells were conducted to generate the tumor immune cell score (TICS) for prognostic stratification. Other two independent cohorts including 188 patients were then used to validate the model. Those patients who underwent chemotherapy were used to further analyze the value of TICS for predicting the chemotherapy response. Furthermore, the difference in the somatic mutations and immune-related molecules between the TICS subgroups was analyzed.Results6 out of 28 immune cells were found to be significantly associated with PDAC prognosis in the training cohorts (all P < 0.05). The developed TICS could significantly predict the PDAC survival and chemotherapy benefit both in the training and the external validation cohorts (log-rank test, P < 0.05). Significant differences were found in different TICS subgroups in terms of the immune characteristics, checkpoint genes, and tumor mutational burden. Functional and pathway analyses further proved that the TICS was significantly related to the tumor immunity response in patients with PDAC.ConclusionTICS might be used to predict PDAC patients with a better survival and greater chemotherapy benefit.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer-related deaths worldwide and it consists of almost 90% pancreatic cancers [1, 2]
The prognostic stratification of a resected PDAC is based on the 8th edition of the AJCC–TNM classification [7], which mostly relies on the tumor invasion parameters containing tumor burden (T), the influence of cancer cells in lymph nodes (N), and presence of metastases (M)
We conducted a prognostic analysis for the 28 immune cells in each training cohort and performed a meta-analysis to obtain these stable and pooled hazard ratio (HR) and coefficients of all 28 immune cells (Supplementary Table S2)
Summary
Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer-related deaths worldwide and it consists of almost 90% pancreatic cancers [1, 2]. In recent years significant improvements have been achieved in the diagnosis and treatment of different kinds of cancers [3], the mortality rate of PDAC has not experienced substantial changes during the Immune Cells Signature Predict OS and Chemosensitivity of PDAC past decades. This is because PDAC is a highly destructive cancer with an extraordinarily high malignancy and a poor prognosis [4]. Given its poor prognosis among cancer and despite combining the advances in surgical techniques and other adjuvant therapy in recent years, the tumor recurrence rate remains at 80% [6]. The effective and accurate stratification of patients with PDAC for prognosis and chemotherapy response is of great importance
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
