title: Prognostic significance of immune cells in the tumor microenvironment and peripheral blood of gallbladder carcinoma patients.
abstract: BACKGROUND
  The role of the interaction between tumor cells and inflammatory cells in gallbladder carcinoma (GBC) is unclear. Inflammatory cells exist in both the tumor immune microenvironment and the host peripheral blood circulatory system. In the current study, we examined the prognostic value of inflammatory cells in the tumor microenvironment and peripheral blood in patients with GBC.
  
  
  METHODS
  98 patients with GBC were recruited in this retrospective study. Using immunohistochemistry, we examined tumor-infiltrating CD3+ generic T-cells, CD8+ cytotoxic T-cells, CD45RO+ memory T-cells, and CD15+ neutrophils. Peripheral venous blood samples were also collected, and absolute neutrophil count (ANC), absolute lymphocyte count (ALC) and neutrophil/lymphocyte ratio (NLR) were measured. The relationships between these variables and patient outcome were evaluated.
  
  
  RESULTS
  Survival analysis revealed that the density of CD3+ cell infiltrates in the tumor microenvironment was positively correlated with overall survival (OS) and the density of CD15+ cell infiltrates was negatively correlated with the OS. The combined analysis showed that a high density of CD3+ cell infiltrates combined with a low density of CD15+ cell infiltrates was an independent prognostic factor for GBC. In peripheral blood, survival analysis suggested that ANC and NLR were negatively correlated, while ALC was positively correlated with OS. Multivariate survival analysis showed that NLR was an independent prognostic factor for gallbladder cancer prognosis.
  
  
  CONCLUSIONS
  The results indicate that the combination of high density of CD3+ cell infiltrates combined with a low density of CD15+ cell infiltrates in tumor samples and pretreatment peripheral blood NLR were independent prognostic factors in patients with GBC.
authors.affiliation: Department of Oncology, School of Medicine, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266011, Shandong, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, 250012, Shandong, People's Republic of China.
authors.forename: C
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Oncology, School of Medicine, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266011, Shandong, People's Republic of China.
authors.forename: M
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Oncology, School of Medicine, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266011, Shandong, People's Republic of China.
authors.forename: H
authors.initials: H
authors.lastname: Hou
authors.affiliation: Department of Pathology, School of Medicine, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266011, Shandong, People's Republic of China.
authors.forename: L
authors.initials: L
authors.lastname: Cui
authors.affiliation: Department of Pathology, School of Medicine, Qingdao Municipal Hospital, Qingdao University, Qingdao, 266011, Shandong, People's Republic of China.
authors.forename: C
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, 250012, Shandong, People's Republic of China.
authors.forename: J
authors.initials: J
authors.lastname: Sun
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, 250012, Shandong, People's Republic of China. xunqu0809@163.com.
authors.forename: X
authors.identifier: http://orcid.org/0000-0002-8276-1692
authors.initials: X
authors.lastname: Qu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000276:immunology* / Q000556:secondary; D005260:Female; D005500:Follow-Up Studies; D005706:Gallbladder Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000097:blood / Q000276:immunology* / Q000473:pathology; D008207:Lymphatic Metastasis; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009504:Neutrophils / Q000276:immunology; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D059016:Tumor Microenvironment / Q000276:immunology*
keywords: Gallbladder carcinoma; Immunohistochemistry; Neutrophil/lymphocyte ratio; Tumor microenvironment; Tumor-infiltrating lymphocytes