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Regulatory T Cell Infiltration Predicts Outcome Following Resection of Colorectal Cancer Liver Metastases

  • Hepatobiliary Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Tumor-infiltrating lymphocyte (TIL) counts in colorectal cancer liver metastases (CRCLM) predict survival following resection. While CD4 and CD8 T cells have been correlated with outcome following CRCLM resection, the role of regulatory T cells (Treg) is not well defined.

Methods

TIL in 188 patients who underwent CRCLM resection between 1998 and 2000 were analyzed by immunohistochemistry using tissue microarrays. Correlation between TIL composition and outcome was determined while controlling for established prognostic factors. Total T cells (CD3), helper T cells (CD4), cytotoxic T cells (CD8), and Treg (FoxP3) were analyzed.

Results

Median follow-up time was 40 months for all patients and 95 months for survivors. Overall survival (OS) at 5 and 10 years was 40 and 25 %, respectively. The CD4 T cell count correlated with OS (p = .02) and recurrence-free survival (p = .04). A high number of CD8 T cells relative to total T cells (CD8:CD3 ratio) predicted longer OS times (p = .05). Analysis of Treg revealed that high FoxP3:CD4 (p = .03) and FoxP3:CD8 (p = .05) ratios were independent predictors of shorter OS. Patients with a high clinical risk score (CRS) were more likely to have a high number of intratumoral Treg, and patients ≥65 years old had a less robust CRCLM T cell infiltration.

Conclusions

A high number of Treg relative to CD4 or CD8 T cells predicted poor outcome, suggesting an immunosuppressive role for FoxP3 + TIL. The intratumoral immune response was an independent predictor of outcome in patients with colorectal liver metastases.

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Authors and Affiliations

  1. Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Steven C. Katz MD, Zubin M. Bamboat MD, Ajay V. Maker MD, Venu G. Pillarisetty MD, Adam C. Yopp MD, William R. Jarnagin MD, Yuman Fong MD, Michael I. D’Angelica MD & Ronald P. DeMatteo MD

  2. Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Jinru Shia MD & Cyrus V. Hedvat MD, PhD

  3. Department of Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Mithat Gonen PhD

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  1. Steven C. Katz MD
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  2. Zubin M. Bamboat MD
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Correspondence to Steven C. Katz MD.

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Katz, S.C., Bamboat, Z.M., Maker, A.V. et al. Regulatory T Cell Infiltration Predicts Outcome Following Resection of Colorectal Cancer Liver Metastases. Ann Surg Oncol 20, 946–955 (2013). https://doi.org/10.1245/s10434-012-2668-9

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  • DOI: https://doi.org/10.1245/s10434-012-2668-9

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