title: Differential impact of tumor-infiltrating immune cells on basal and luminal cells: implications for tumor invasion and metastasis.
abstract: OBJECTIVE
  Regarding the impact of tumor-infiltrating immune cells on tumor cells, many contradictory reports have been published. We have hypothesized that these controversies result from differences in tissue types and tumor stages, in which immune cells are variably distributed and differentially associated with epithelial cells. Our current study compared the pattern and frequency of physical association of tumor-infiltrating immune cells with different parenchymal cells of human breast and prostate tumors harboring normal, hyperplastic, in situ, and invasive components.
  
  
  METHODS
  The cytological, biological, and molecular alterations were assessed with double immunohistochemistry, double fluorescent labeling, apoptosis assay, and gene expression profiling.
  
  
  RESULTS
  Our study detected several previously undescribed features: (i) over 95% of infiltrating immune cells were seen within normal, hyperplastic, or in situ cancer structures with focally-disrupted capsules, and fewer than 5% were found within invasive cancer; (ii) over 95% of normal, hyperplastic, and in situ cancerous epithelial cells were physically shielded from immune cells by the surrounding myoepithelial or basal cell layer; (iii) about 90% of myoepithelial or basal cells physically associated with immune cells and such residual cells within focally disrupted layers exhibited distinct degeneration, including apoptosis, necrosis, and reduced expression of tumor suppressor p63; (iv) epithelial cells overlying focally disrupted tumor capsules surrounded by immune cells had substantially higher proliferation than their adjacent counterparts, and some of the proliferating cells were arranged as tongue-like projections invading the stroma; and (v) microdissected cells overlying focally disrupted tumor capsules had more than 5-fold higher expression of stem cell lineage markers KIT and NCOR2.
  
  
  CONCLUSIONS
  Tumor-infiltrating immune cells are primarily associated with degenerated myoepithelial or basal cells causing focal disruptions of the capsule, which selectively favor proliferation, invasion, and dissemination of the overlying tumor stem cells.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Breast Oncology, Peking University Cancer Hospital & Institute, Beijing, R.O.C. songguohong918@hotmail.com yanmann@aol.com yangao_man@bshsi.org.
authors.forename: Guohong
authors.initials: G
authors.lastname: Song
authors.affiliation: School of Medicine, Chung Shan Medical University, Taichung, Taiwan, R.O.C. Department of Obstetrics and Gynecology, Changhua Christian Hospital, Changhua, Taiwan, R.O.C.
authors.forename: Hsuan
authors.initials: H
authors.lastname: Hsiao
authors.affiliation: Genetic and Genomics Department, Icahn Mount Sinai Medical School, New York, NY, U.S.A.
authors.forename: Jinlian L
authors.initials: JL
authors.lastname: Wang
authors.affiliation: Department of Pathology, Hackensack University Medical Center, Hackensack, NJ, U.S.A.
authors.forename: Ciaran
authors.initials: C
authors.lastname: Mannion
authors.affiliation: Bon Secours Cancer Institute, Bon Secours Health System, Richmond, VA, U.S.A.
authors.forename: Alexander
authors.initials: A
authors.lastname: Stojadinovic
authors.affiliation: Bon Secours Cancer Institute, Bon Secours Health System, Richmond, VA, U.S.A.
authors.forename: Itzhak
authors.initials: I
authors.lastname: Avital
authors.affiliation: Department of Medicine, The George Washington University Medical Center, Washington, DC, U.S.A. Department of Microbiology, Immunology & Tropical Medicine, The George Washington University Medical Center, Washington, DC, U.S.A.
authors.forename: Sidney W
authors.initials: SW
authors.lastname: Fu
authors.affiliation: Laboratory of Proteomics and Protein Science, Veterans Affairs Medical Center, Baltimore, MD, U.S.A.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Mason
authors.affiliation: Department of Pathology, Veterans Affairs Medical Center, Washington, DC, U.S.A.
authors.forename: Wen
authors.initials: W
authors.lastname: Chen
authors.affiliation: Tumor Immunology Laboratory, Division of Oral Biology and Medicine, Jonsson Comprehensive Cancer Center, UCLA School of Dentistry, Los Angeles, CA, U.S.A.
authors.forename: Anahid
authors.initials: A
authors.lastname: Jewett
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Breast Oncology, Peking University Cancer Hospital & Institute, Beijing, R.O.C.
authors.forename: Huiping
authors.initials: H
authors.lastname: Li
authors.affiliation: Bon Secours Cancer Institute, Bon Secours Health System, Richmond, VA, U.S.A. songguohong918@hotmail.com yanmann@aol.com yangao_man@bshsi.org.
authors.forename: Yan-Gao
authors.initials: YG
authors.lastname: Man
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001940:Breast / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D001943:Breast Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D002280:Basal Cell Carcinoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011467:Prostate / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger
keywords: Tumor-infiltrating immune cells; basal cells; degeneration; proliferation; stem cells