Regulatory T cell infiltration predicts outcome following resection of colorectal cancer liver metastases

Steven C. Katz, Zubin M. Bamboat, Ajay V. Maker, Jinru Shia, Venu G. Pillarisetty, Adam C. Yopp, Cyrus V. Hedvat, Mithat Gonen, William R. Jarnagin, Yuman Fong, Michael I. D'Angelica, Ronald P. Dematteo

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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.

Original languageEnglish (US)
Pages (from-to)946-955
Number of pages10
JournalAnnals of Surgical Oncology
Volume20
Issue number3
DOIs
StatePublished - Mar 2013

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Regulatory T-Lymphocytes
Liver Neoplasms
Colorectal Neoplasms
Neoplasm Metastasis
T-Lymphocytes
Tumor-Infiltrating Lymphocytes
Survival
Lymphocyte Count
Immunosuppressive Agents
CD4 Lymphocyte Count
Helper-Inducer T-Lymphocytes
Survivors
Immunohistochemistry
Recurrence
Liver

ASJC Scopus subject areas

  • Surgery
  • Oncology

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Regulatory T cell infiltration predicts outcome following resection of colorectal cancer liver metastases. / Katz, Steven C.; Bamboat, Zubin M.; Maker, Ajay V.; Shia, Jinru; Pillarisetty, Venu G.; Yopp, Adam C.; Hedvat, Cyrus V.; Gonen, Mithat; Jarnagin, William R.; Fong, Yuman; D'Angelica, Michael I.; Dematteo, Ronald P.

In: Annals of Surgical Oncology, Vol. 20, No. 3, 03.2013, p. 946-955.

Research output: Contribution to journalArticle

Katz, SC, Bamboat, ZM, Maker, AV, Shia, J, Pillarisetty, VG, Yopp, AC, Hedvat, CV, Gonen, M, Jarnagin, WR, Fong, Y, D'Angelica, MI & Dematteo, RP 2013, 'Regulatory T cell infiltration predicts outcome following resection of colorectal cancer liver metastases', Annals of Surgical Oncology, vol. 20, no. 3, pp. 946-955. https://doi.org/10.1245/s10434-012-2668-9
Katz, Steven C. ; Bamboat, Zubin M. ; Maker, Ajay V. ; Shia, Jinru ; Pillarisetty, Venu G. ; Yopp, Adam C. ; Hedvat, Cyrus V. ; Gonen, Mithat ; Jarnagin, William R. ; Fong, Yuman ; D'Angelica, Michael I. ; Dematteo, Ronald P. / Regulatory T cell infiltration predicts outcome following resection of colorectal cancer liver metastases. In: Annals of Surgical Oncology. 2013 ; Vol. 20, No. 3. pp. 946-955.
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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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T1 - Regulatory T cell infiltration predicts outcome following resection of colorectal cancer liver metastases

AU - Katz, Steven C.

AU - Bamboat, Zubin M.

AU - Maker, Ajay V.

AU - Shia, Jinru

AU - Pillarisetty, Venu G.

AU - Yopp, Adam C.

AU - Hedvat, Cyrus V.

AU - Gonen, Mithat

AU - Jarnagin, William R.

AU - Fong, Yuman

AU - D'Angelica, Michael I.

AU - Dematteo, Ronald P.

PY - 2013/3

Y1 - 2013/3

N2 - 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.

AB - 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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