Cancer Immunology, Immunotherapy

, Volume 59, Issue 5, pp 653–661 | Cite as

Intratumoral CD8+ T/FOXP3+ cell ratio is a predictive marker for survival in patients with colorectal cancer

  • Hiroyuki Suzuki
  • Nobuhito Chikazawa
  • Takehiko Tasaka
  • Junji Wada
  • Akio Yamasaki
  • Yoshiki Kitaura
  • Masae Sozaki
  • Masao Tanaka
  • Hideya Onishi
  • Takashi Morisaki
  • Mitsuo KatanoEmail author
Original Article


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-β 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-β may contribute to the increased number of itFOXP3+ cells.


Colorectal cancer Intratumoral CD8+ T cells Intratumoral FOXP3+ regulatory T cells CD8+ T cell/FOXP3+ cell ratio Prognostic factor 



CD4+ regulatory T cells


Forkhead box P3

itCD8+ T cells

Intratumoral CD8-positive T cells

itFOXP3+ cells

Intratumoral FOXP3-positive cells

itCD8+ T/itFOXP3+ cell ratio

Ratio of number of intratumoral CD8-positive T cells to number of intratumoral FOXP3-positive cells


Tumor-infiltrating lymphocytes


Peripheral blood mononuclear cells


Transforming growth factor-beta



This study was supported by a General Scientific Research Grant (18591440) from Ministry of Education, Culture, Sports, Science and Technology of Japan. We thank Kaori Nomiyama for skillful technical assistance.


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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Hiroyuki Suzuki
    • 1
  • Nobuhito Chikazawa
    • 1
  • Takehiko Tasaka
    • 1
  • Junji Wada
    • 1
  • Akio Yamasaki
    • 1
  • Yoshiki Kitaura
    • 1
  • Masae Sozaki
    • 1
  • Masao Tanaka
    • 2
  • Hideya Onishi
    • 1
  • Takashi Morisaki
    • 1
  • Mitsuo Katano
    • 1
    Email author
  1. 1.Department of Cancer Therapy and Research, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  2. 2.Department of Surgery and Oncology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan

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