title: Systemic Immune Activity Predicts Overall Survival in Treatment-Naïve Patients with Metastatic Pancreatic Cancer.
abstract: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a 5-year survival rate <7% and is ultimately refractory to most treatments. To date, an assessment of immunologic factors relevant to disease has not been comprehensively performed for treatment-naïve patients. We hypothesized that systemic immunologic biomarkers could predict overall survival (OS) in treatment-naïve PDAC patients.
  
  
  
  Peripheral blood was collected from 73 patients presenting with previously untreated metastatic PDAC. Extensive immunologic profiling was conducted to assess relationships between OS and the level of soluble plasma biomarkers or detailed immune cell phenotypes as measured by flow cytometry.
  
  
  
  Higher baseline levels of the immunosuppressive cytokines IL6 and IL10 were strongly associated with poorer OS (P = 0.008 and 0.026, respectively; HR = 1.16 and 1.28, respectively), whereas higher levels of the monocyte chemoattractant MCP-1 were associated with significantly longer OS (P = 0.045; HR = 0.69). Patients with a greater proportion of antigen-experienced T cells (CD45RO(+)) had longer OS (CD4 P = 0.032; CD8 P = 0.036; HR = 0.36 and 0.61, respectively). Although greater expression of the T-cell checkpoint molecule CTLA-4 on CD8(+) T cells was associated with significantly shorter OS (P = 0.020; HR = 1.53), the TIM3 molecule had a positive association with survival when expressed on CD4(+) T cells (P = 0.046; HR = 0.62).
  
  
  
  These data support the hypothesis that baseline immune status predicts PDAC disease course and overall patient survival. To our knowledge, this work represents the largest cohort and most comprehensive immune profiling of treatment-naïve metastatic PDAC patients to date. Clin Cancer Res; 22(10); 2565-74. ©2015 AACR.
authors.affiliation: Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Farren
authors.affiliation: Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Mace
authors.affiliation: Health Informatics Institute, University of South Florida, Tampa, Florida.
authors.forename: Susan
authors.initials: S
authors.lastname: Geyer
authors.affiliation: Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
authors.forename: Sameh
authors.initials: S
authors.lastname: Mikhail
authors.affiliation: Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
authors.forename: Christina
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
authors.forename: Kristen
authors.initials: K
authors.lastname: Ciombor
authors.affiliation: Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
authors.forename: Sanaa
authors.initials: S
authors.lastname: Tahiri
authors.affiliation: Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ahn
authors.affiliation: Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Noonan
authors.affiliation: Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
authors.forename: Miguel
authors.initials: M
authors.lastname: Villalona-Calero
authors.affiliation: Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
authors.forename: Tanios
authors.initials: T
authors.lastname: Bekaii-Saab
authors.affiliation: Department of Internal Medicine, The Ohio State University, Columbus, Ohio. Gregory.Lesinski@osumc.edu.
authors.forename: Gregory B
authors.initials: GB
authors.lastname: Lesinski
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D060908:CTLA-4 Antigen / Q000276:immunology; D021441:Carcinoma, Pancreatic Ductal / Q000276:immunology / Q000401:mortality; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D010179:Pancreas / Q000276:immunology; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000401:mortality*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D060908:CTLA-4 Antigen; D015850:Interleukin-6; D016753:Interleukin-10