title: A High RORγT/CD3 Ratio is a Strong Prognostic Factor for Postoperative Survival in Advanced Colorectal Cancer: Analysis of Helper T Cell Lymphocytes (Th1, Th2, Th17 and Regulatory T Cells).
abstract: BACKGROUND
  Tumor-infiltrating lymphocytes (TILs), part of the host immune response, have been widely reported as influential factors in the tumor microenvironment for the clinical outcome of colorectal cancer (CRC). However, the network of helper T cells is very complex, and which T-cell subtypes affect the progression of CRC and postoperative prognosis remains unclear. This study investigated the expression of several subtypes of TILs including T helper type 1 (Th1), Th2, Th17, and regulatory T (Treg) cells to determine their correlation with clinicopathologic features and postoperative prognosis.
  
  
  METHODS
  The study investigated the expression of TILs using immunohistochemistry of tissue microarray samples for 199 CRC patients. The number of each T-cell subtype infiltrating tumors was counted using ImageJ software. The relationship between TIL marker expression, clinicopathologic features, and prognosis was analyzed.
  
  
  RESULTS
  A high RORγT/CD3 ratio (Th17 ratio) was significantly correlated with lymph node metastasis (p = 0.002), and a high of Foxp3/CD3 ratio (Treg ratio) was correlated with tumor location in the colon (p = 0.04), as shown by the Chi square test. In multivariate analysis, a high RORγT/CD3 ratio was the only independent prognostic factor for overall survival (p = 0.04; hazard ratio [HR], 1.84; 95% confidence interval [CI] 1.02-3.45).
  
  
  CONCLUSIONS
  This study confirmed a high RORγT/CD3 ratio as a strong prognostic marker for postoperative survival. The immunohistochemistry results suggest that Th17 may affect lymph node metastasis in CRC. If new immunotherapies reducing Th17 expression are established, they may improve the efficiency of cancer treatment and prolong the survival of patients with CRC.
authors.affiliation: Department of Surgery, Kurume University School of Medicine, Kurume-shi, Fukuoka, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Yoshida
authors.affiliation: Department of Surgery, Kurume University School of Medicine, Kurume-shi, Fukuoka, Japan. kinugasa_tetsushi@med.kurume-u.ac.jp.
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Kinugasa
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Miyoshi
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Kensaku
authors.initials: K
authors.lastname: Sato
authors.affiliation: Department of Surgery, Kurume University School of Medicine, Kurume-shi, Fukuoka, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Yuge
authors.affiliation: Department of Surgery, Kurume University School of Medicine, Kurume-shi, Fukuoka, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ohchi
authors.affiliation: Department of Surgery, Kurume University School of Medicine, Kurume-shi, Fukuoka, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Fujino
authors.affiliation: Department of Surgery, Kurume University School of Medicine, Kurume-shi, Fukuoka, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Shiraiwa
authors.affiliation: Department of Surgery, Kurume University School of Medicine, Kurume-shi, Fukuoka, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Katagiri
authors.affiliation: Department of Surgery, Kurume University School of Medicine, Kurume-shi, Fukuoka, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Akagi
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Ohshima
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D017252:CD3 Complex / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015179:Colorectal Neoplasms / Q000276:immunology / Q000378:metabolism / Q000401:mortality* / Q000556:secondary; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000276:immunology / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism*; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D017252:CD3 Complex; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539900:RORC protein, human