title: LAP+CD4+ T cells are suppressors accumulated in the tumor sites and associated with the progression of colorectal cancer.
abstract: OBJECTIVE
  Suppressor T cells are one of the determinants of colorectal cancer (CRC) clinical outcome. LAP(+)CD4(+) T cell is a recently identified subset of suppressor T cells. This study was designed to investigate their clinical relevance in patients with CRC.
  
  
  METHODS
  Sixty patients with CRC and 24 healthy donors (HD) were enrolled in this study. The percentages of LAP(+)CD4(+) T cells in peripheral blood and tumor tissue were measured. The phenotype and functional relevance of LAP(+)CD4(+) T cells were analyzed subsequently.
  
  
  RESULTS
  The percentages of LAP(+)CD4(+) T cells in peripheral blood of patients with CRC were significantly higher than HD (HD vs. CRC: 3.1% ± 0.78% vs. 8.8% ± 5.8%, P < 0.0001) and in tumor tissue when compared with nontumor tissue (nontumor vs. tumor: 3.2% ± 1.1% vs. 9.5% ± 5.5%, P = 0.0002). In addition, LAP(+)CD4(+) T cells with effector memory (EM) phenotype were more likely to accumulate in the tumor sites than in peripheral blood. These LAP(+)CD4(+) T cells produced significantly higher levels of IFN-γ, IL-17 and comparatively lower IL-2 and very few IL-10. LAP(+)CD4(+) T cells could suppress the proliferation of LAP(-)CD4(+) T cells that were partially mediated by TGF-β. Furthermore, these LAP(+)CD4(+) T cells accumulated in tumor site and increased further in the peripheral blood in patients with metastasis.
  
  
  CONCLUSIONS
  LAP(+)CD4(+) T cells as a suppressor subset could accumulate in the tumor microenvironment and circulated more in the peripheral blood with tumor progression in patients with CRC.
authors.affiliation: Department of Gastroenterology-Hepatology, Chang Gung University, Kweishan, Tayouan, Taiwan.
authors.forename: Jayashri
authors.initials: J
authors.lastname: Mahalingam
authors.forename: Yung-Chang
authors.initials: YC
authors.lastname: Lin
authors.forename: Jy-Ming
authors.initials: JM
authors.lastname: Chiang
authors.forename: Po-Jung
authors.initials: PJ
authors.lastname: Su
authors.forename: Jian-He
authors.initials: JH
authors.lastname: Fang
authors.forename: Yu-Yi
authors.initials: YY
authors.lastname: Chu
authors.forename: Ching-Tai
authors.initials: CT
authors.lastname: Huang
authors.forename: Cheng-Tang
authors.initials: CT
authors.lastname: Chiu
authors.forename: Chun-Yen
authors.initials: CY
authors.lastname: Lin
mesh_terms: D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D015179:Colorectal Neoplasms / Q000097:blood / Q000276:immunology / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010455:Peptides / Q000097:blood / Q000276:immunology; D011498:Protein Precursors / Q000097:blood / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000097:blood / Q000276:immunology; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: D010455:Peptides; D011498:Protein Precursors; D016212:Transforming Growth Factor beta; C472416:latency-associated propeptide, TGF-beta