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

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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-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.

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Abbreviations

Tregs:

CD4+ regulatory T cells

FOXP3:

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

TILs:

Tumor-infiltrating lymphocytes

PBMCs:

Peripheral blood mononuclear cells

TGF-β:

Transforming growth factor-beta

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Acknowledgments

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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Authors and Affiliations

  1. Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan

    Hiroyuki Suzuki, Nobuhito Chikazawa, Takehiko Tasaka, Junji Wada, Akio Yamasaki, Yoshiki Kitaura, Masae Sozaki, Hideya Onishi, Takashi Morisaki & Mitsuo Katano

  2. Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Masao Tanaka

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  1. Hiroyuki Suzuki
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  2. Nobuhito Chikazawa
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Correspondence to Mitsuo Katano.

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Suzuki, H., Chikazawa, N., Tasaka, T. et al. Intratumoral CD8+ T/FOXP3+ cell ratio is a predictive marker for survival in patients with colorectal cancer. Cancer Immunol Immunother 59, 653–661 (2010). https://doi.org/10.1007/s00262-009-0781-9

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  • DOI: https://doi.org/10.1007/s00262-009-0781-9

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