Tumor-infiltrating Foxp3-CD4+CD25+ T cells predict poor survival in renal cell carcinoma

Sameer A. Siddiqui, Xavier Frigola, Sandra Bonne-Annee, Maria Mercader, Susan M. Kuntz, Amy Krambeck, Shomik Sengupta, Haidong Dong, John C. Cheville, Christine M. Lohse, Christopher J. Krco, W. Scott Webster, Bradley C. Leibovich, Michael L. Blute, Keith L. Knutson, Eugene D. Kwon

Research output: Contribution to journalArticle

130 Citations (Scopus)

Abstract

Purpose: Regulatory T cells (Tregs) have been implicated as inhibitors of antitumoral immunity, and evidence suggests that elimination of Tregs may augment natural and pharmacologic immunity. We tested for the presence of putative Tregs within renal cell carcinoma (RCC) tumors. Experimental Design: We identified 170 patients who underwent radical or partial nephrectomy for clear cell RCC between 2000 and 2002. Specimens were stained with anti-CD4, anti-CD25, and anti-Foxp3 antibodies and examined using confocal microscopy. Associations of CD4+CD25+Foxp3- and CD4+CD25 +Foxp3+ T cells with death from RCC were evaluated using Cox proportional hazards regression models. Results: At last follow-up, 46 of 170 patients had died; of these, 37 died from RCC at a median of 1.4 years following nephrectomy (range, 0-4.4). Among the 124 remaining patients, median follow-up was 3.7 years (range, 0-5.7). Forty-three (25.3%) tumors harbored CD4+CD25+Foxp3+ T cells. The presence of Foxp3+ T cells was not significantly associated with RCC death univariately. One hundred forty-three (84.1%) tumors harbored CD4 +CD25+Foxp3- T cells. The indicator for ≥10% CD4+CD25+Foxp3- T cells was significantly associated with RCC death univariately [risk ratio (RR), 2.60; 95% confidence interval (95% CI), 1.35-4.98; P = 0.004], after adjusting for tumor B7-H1 expression (RR, 2.53; 95% CI, 1.32-4.85; P = 0.005) and lymphocytic infiltration (RR, 2.53; 95% CI, 1.32-4.87; P = 0.005). Conclusions: Increased presence of CD4+CD25+Foxp3+ T cells was not significantly associated with RCC death. In contrast, CD4+CD25 +Foxp3- T cells, which may represent a unique set of Tregs or activated helper T cells, was significantly associated with outcome.

Original languageEnglish (US)
Pages (from-to)2075-2081
Number of pages7
JournalClinical Cancer Research
Volume13
Issue number7
DOIs
StatePublished - Apr 1 2007
Externally publishedYes

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Renal Cell Carcinoma
T-Lymphocytes
Survival
Cell Death
Neoplasms
Odds Ratio
Confidence Intervals
Nephrectomy
Regulatory T-Lymphocytes
Helper-Inducer T-Lymphocytes
Proportional Hazards Models
Innate Immunity
Confocal Microscopy
Anti-Idiotypic Antibodies
Immunity
Research Design

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Siddiqui, S. A., Frigola, X., Bonne-Annee, S., Mercader, M., Kuntz, S. M., Krambeck, A., ... Kwon, E. D. (2007). Tumor-infiltrating Foxp3-CD4+CD25+ T cells predict poor survival in renal cell carcinoma. Clinical Cancer Research, 13(7), 2075-2081. https://doi.org/10.1158/1078-0432.CCR-06-2139

Tumor-infiltrating Foxp3-CD4+CD25+ T cells predict poor survival in renal cell carcinoma. / Siddiqui, Sameer A.; Frigola, Xavier; Bonne-Annee, Sandra; Mercader, Maria; Kuntz, Susan M.; Krambeck, Amy; Sengupta, Shomik; Dong, Haidong; Cheville, John C.; Lohse, Christine M.; Krco, Christopher J.; Webster, W. Scott; Leibovich, Bradley C.; Blute, Michael L.; Knutson, Keith L.; Kwon, Eugene D.

In: Clinical Cancer Research, Vol. 13, No. 7, 01.04.2007, p. 2075-2081.

Research output: Contribution to journalArticle

Siddiqui, SA, Frigola, X, Bonne-Annee, S, Mercader, M, Kuntz, SM, Krambeck, A, Sengupta, S, Dong, H, Cheville, JC, Lohse, CM, Krco, CJ, Webster, WS, Leibovich, BC, Blute, ML, Knutson, KL & Kwon, ED 2007, 'Tumor-infiltrating Foxp3-CD4+CD25+ T cells predict poor survival in renal cell carcinoma', Clinical Cancer Research, vol. 13, no. 7, pp. 2075-2081. https://doi.org/10.1158/1078-0432.CCR-06-2139
Siddiqui, Sameer A. ; Frigola, Xavier ; Bonne-Annee, Sandra ; Mercader, Maria ; Kuntz, Susan M. ; Krambeck, Amy ; Sengupta, Shomik ; Dong, Haidong ; Cheville, John C. ; Lohse, Christine M. ; Krco, Christopher J. ; Webster, W. Scott ; Leibovich, Bradley C. ; Blute, Michael L. ; Knutson, Keith L. ; Kwon, Eugene D. / Tumor-infiltrating Foxp3-CD4+CD25+ T cells predict poor survival in renal cell carcinoma. In: Clinical Cancer Research. 2007 ; Vol. 13, No. 7. pp. 2075-2081.
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abstract = "Purpose: Regulatory T cells (Tregs) have been implicated as inhibitors of antitumoral immunity, and evidence suggests that elimination of Tregs may augment natural and pharmacologic immunity. We tested for the presence of putative Tregs within renal cell carcinoma (RCC) tumors. Experimental Design: We identified 170 patients who underwent radical or partial nephrectomy for clear cell RCC between 2000 and 2002. Specimens were stained with anti-CD4, anti-CD25, and anti-Foxp3 antibodies and examined using confocal microscopy. Associations of CD4+CD25+Foxp3- and CD4+CD25 +Foxp3+ T cells with death from RCC were evaluated using Cox proportional hazards regression models. Results: At last follow-up, 46 of 170 patients had died; of these, 37 died from RCC at a median of 1.4 years following nephrectomy (range, 0-4.4). Among the 124 remaining patients, median follow-up was 3.7 years (range, 0-5.7). Forty-three (25.3{\%}) tumors harbored CD4+CD25+Foxp3+ T cells. The presence of Foxp3+ T cells was not significantly associated with RCC death univariately. One hundred forty-three (84.1{\%}) tumors harbored CD4 +CD25+Foxp3- T cells. The indicator for ≥10{\%} CD4+CD25+Foxp3- T cells was significantly associated with RCC death univariately [risk ratio (RR), 2.60; 95{\%} confidence interval (95{\%} CI), 1.35-4.98; P = 0.004], after adjusting for tumor B7-H1 expression (RR, 2.53; 95{\%} CI, 1.32-4.85; P = 0.005) and lymphocytic infiltration (RR, 2.53; 95{\%} CI, 1.32-4.87; P = 0.005). Conclusions: Increased presence of CD4+CD25+Foxp3+ T cells was not significantly associated with RCC death. In contrast, CD4+CD25 +Foxp3- T cells, which may represent a unique set of Tregs or activated helper T cells, was significantly associated with outcome.",
author = "Siddiqui, {Sameer A.} and Xavier Frigola and Sandra Bonne-Annee and Maria Mercader and Kuntz, {Susan M.} and Amy Krambeck and Shomik Sengupta and Haidong Dong and Cheville, {John C.} and Lohse, {Christine M.} and Krco, {Christopher J.} and Webster, {W. Scott} and Leibovich, {Bradley C.} and Blute, {Michael L.} and Knutson, {Keith L.} and Kwon, {Eugene D.}",
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T1 - Tumor-infiltrating Foxp3-CD4+CD25+ T cells predict poor survival in renal cell carcinoma

AU - Siddiqui, Sameer A.

AU - Frigola, Xavier

AU - Bonne-Annee, Sandra

AU - Mercader, Maria

AU - Kuntz, Susan M.

AU - Krambeck, Amy

AU - Sengupta, Shomik

AU - Dong, Haidong

AU - Cheville, John C.

AU - Lohse, Christine M.

AU - Krco, Christopher J.

AU - Webster, W. Scott

AU - Leibovich, Bradley C.

AU - Blute, Michael L.

AU - Knutson, Keith L.

AU - Kwon, Eugene D.

PY - 2007/4/1

Y1 - 2007/4/1

N2 - Purpose: Regulatory T cells (Tregs) have been implicated as inhibitors of antitumoral immunity, and evidence suggests that elimination of Tregs may augment natural and pharmacologic immunity. We tested for the presence of putative Tregs within renal cell carcinoma (RCC) tumors. Experimental Design: We identified 170 patients who underwent radical or partial nephrectomy for clear cell RCC between 2000 and 2002. Specimens were stained with anti-CD4, anti-CD25, and anti-Foxp3 antibodies and examined using confocal microscopy. Associations of CD4+CD25+Foxp3- and CD4+CD25 +Foxp3+ T cells with death from RCC were evaluated using Cox proportional hazards regression models. Results: At last follow-up, 46 of 170 patients had died; of these, 37 died from RCC at a median of 1.4 years following nephrectomy (range, 0-4.4). Among the 124 remaining patients, median follow-up was 3.7 years (range, 0-5.7). Forty-three (25.3%) tumors harbored CD4+CD25+Foxp3+ T cells. The presence of Foxp3+ T cells was not significantly associated with RCC death univariately. One hundred forty-three (84.1%) tumors harbored CD4 +CD25+Foxp3- T cells. The indicator for ≥10% CD4+CD25+Foxp3- T cells was significantly associated with RCC death univariately [risk ratio (RR), 2.60; 95% confidence interval (95% CI), 1.35-4.98; P = 0.004], after adjusting for tumor B7-H1 expression (RR, 2.53; 95% CI, 1.32-4.85; P = 0.005) and lymphocytic infiltration (RR, 2.53; 95% CI, 1.32-4.87; P = 0.005). Conclusions: Increased presence of CD4+CD25+Foxp3+ T cells was not significantly associated with RCC death. In contrast, CD4+CD25 +Foxp3- T cells, which may represent a unique set of Tregs or activated helper T cells, was significantly associated with outcome.

AB - Purpose: Regulatory T cells (Tregs) have been implicated as inhibitors of antitumoral immunity, and evidence suggests that elimination of Tregs may augment natural and pharmacologic immunity. We tested for the presence of putative Tregs within renal cell carcinoma (RCC) tumors. Experimental Design: We identified 170 patients who underwent radical or partial nephrectomy for clear cell RCC between 2000 and 2002. Specimens were stained with anti-CD4, anti-CD25, and anti-Foxp3 antibodies and examined using confocal microscopy. Associations of CD4+CD25+Foxp3- and CD4+CD25 +Foxp3+ T cells with death from RCC were evaluated using Cox proportional hazards regression models. Results: At last follow-up, 46 of 170 patients had died; of these, 37 died from RCC at a median of 1.4 years following nephrectomy (range, 0-4.4). Among the 124 remaining patients, median follow-up was 3.7 years (range, 0-5.7). Forty-three (25.3%) tumors harbored CD4+CD25+Foxp3+ T cells. The presence of Foxp3+ T cells was not significantly associated with RCC death univariately. One hundred forty-three (84.1%) tumors harbored CD4 +CD25+Foxp3- T cells. The indicator for ≥10% CD4+CD25+Foxp3- T cells was significantly associated with RCC death univariately [risk ratio (RR), 2.60; 95% confidence interval (95% CI), 1.35-4.98; P = 0.004], after adjusting for tumor B7-H1 expression (RR, 2.53; 95% CI, 1.32-4.85; P = 0.005) and lymphocytic infiltration (RR, 2.53; 95% CI, 1.32-4.87; P = 0.005). Conclusions: Increased presence of CD4+CD25+Foxp3+ T cells was not significantly associated with RCC death. In contrast, CD4+CD25 +Foxp3- T cells, which may represent a unique set of Tregs or activated helper T cells, was significantly associated with outcome.

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