title: Intratumoral CD8(+) T/FOXP3 (+) cell ratio is a predictive marker for survival in patients with colorectal cancer.
abstract: The human immune system consists of a balance between immune surveillance against non-self antigens and tolerance of self-antigens. CD8(+) T cells and CD4(+) regulatory T cells (Tregs) are the main players for immune surveillance and tolerance, respectively. We examined immunohistochemically the immunological balance at the tumor site using 94 surgically resected colorectal cancer tissues. Forkhead box P3 (FOXP3)(+) cells were considered to be Tregs in the present study. The number of intratumoral FOXP3(+) cells (itFOXP3(+) cells) was positively correlated with lymph node metastases (P = 0.030). itCD8(+) T/itFOXP3(+) cell ratio negatively correlated with pathological stages (P = 0.048). Next, relationship between the number of itCD8(+) T cells or itFOXP3(+) cells and survival prognosis in 94 patients who underwent a curative resection was analyzed. Only itCD8(+) T/itFOXP3(+) cell ratio positively correlated with disease-free survival (0.023) and overall survival (P = 0.010). Multivariate analysis indicated that itCD8(+) T/itFOXP3(+) cell ratio is an independent prognostic factor (P = 0.035) of overall survival. The number of itFOXP3(+) cells positively correlated with transforming growth factor-beta TGF-beta production at the tumor site (P = 0.020). In conclusion, itCD8(+) T/itFOXP3(+) cell ratio is a predictive marker for both disease-free survival time and overall survival time in patients with colorectal cancer. Importantly, itCD8(+) T/itFOXP3(+) cell ratio may be an independent prognostic factor. And, tumor-producing TGF-beta may contribute to the increased number of itFOXP3(+) cells.
authors.affiliation: Department of Cancer Therapy and Research, Kyushu University, Maidashi, Higashi-Ku, Fukuoka, Japan. h-suzuki@surg1.med.kyushu-u.ac.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Suzuki
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Chikazawa
authors.forename: Takehiko
authors.initials: T
authors.lastname: Tasaka
authors.forename: Junji
authors.initials: J
authors.lastname: Wada
authors.forename: Akio
authors.initials: A
authors.lastname: Yamasaki
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kitaura
authors.forename: Masae
authors.initials: M
authors.lastname: Sozaki
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka
authors.forename: Hideya
authors.initials: H
authors.lastname: Onishi
authors.forename: Takashi
authors.initials: T
authors.lastname: Morisaki
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Katano
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002469:Cell Separation; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis / Q000276:immunology / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D016212:Transforming Growth Factor beta