title: Destructive impact of T-lymphocytes, NK and Mast cells on basal cell layers: implications for tumor invasion.
abstract: BACKGROUND
  Our previous studies have suggested that the primary impact of immune cell infiltration into the normal or pre-invasive tissue component is associated with the physical destruction of epithelial capsules, which may promote tumor progression and invasion. Our current study attempted to further verify our previous observations and determine the primary type(s) of infiltrating immune cells and the possible mechanism associated with physical destructions of the epithelial capsules.
  
  
  METHODS
  In total, the study was conducted with 250 primary breast and prostate tumors, the primary immune cell of cytotoxic T-lymphocytes (CTL), Natural killer cells (NK) and Mast cells were analyzed by immunohistochemistry, fluorescent labeling and apoptosis assay. qRT-PCR was used for gene expression analysis. Our current study assessed the physical disruption of these immune cells and potential impact on the epithelial capsule of human breast and prostate tumors.
  
  
  RESULTS
  Our study yield several clinically-relevant findings that have not been studied before. (1) A vast majority of these infiltrating immune cells are distributed in the normal-appearing or pre-invasive tissue components rather than in invasive cancer tissues. (2) These cells often form rings or semilunar structures that either surround focally-disrupted basal cell layers or physically attach to the basal cells. (3) Basal cells physically associated with these immune cells generally displayed distinct signs of degeneration, including substantially elevated apoptosis, necrosis, and reduced tumor suppressor p63 expression. In contrast, luminal cells overlying focally disrupted basal cell layers had a substantially increased proliferation rate and elevated expression of stem cell markers compared to their adjacent morphologically similar counterparts that overlie a non-disrupted capsule.
  
  
  CONCLUSIONS
  Our findings suggest that at the early stage of tumor invasion, CTL, NK and Mast cells are the main types of tumor infiltrating immune cells involved in focal degenerative products in the tumor capsules. The primary impact of these infiltrating immune cells is that they are associated with focal disruptions of the tumor capsule, which selectively favor tumor stem cells proliferation and invasion.
authors.affiliation: Department of Oncology, the Affiliated Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University, Nanjing, China. dryhy@hotmail.com
authors.forename: Hongyan
authors.initials: H
authors.lastname: Yuan
authors.forename: Yi-Hsuan
authors.initials: YH
authors.lastname: Hsiao
authors.forename: Yiyu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jinlian
authors.initials: J
authors.lastname: Wang
authors.forename: Chao
authors.initials: C
authors.lastname: Yin
authors.forename: Rong
authors.initials: R
authors.lastname: Shen
authors.forename: Yiping
authors.initials: Y
authors.lastname: Su
mesh_terms: D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000473:pathology*; D009361:Neoplasm Invasiveness / Q000276:immunology / Q000473:pathology; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology*