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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 9/2009

01-09-2009 | Hepatobiliary and Pancreatic Tumors

T Cell Infiltrate Predicts Long-Term Survival Following Resection of Colorectal Cancer Liver Metastases

Authors: Steven C. Katz, MD, Venu Pillarisetty, MD, Zubin M. Bamboat, MD, Jinru Shia, MD, Cyrus Hedvat, MD, Mithat Gonen, PhD, William Jarnagin, MD, Yuman Fong, MD, Leslie Blumgart, MD, Michael D’Angelica, MD, Ronald P. DeMatteo, MD

Published in: Annals of Surgical Oncology | Issue 9/2009

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Abstract

Background

While tumor infiltrating lymphocytes (TIL) have been shown to independently predict survival in primary colorectal cancer, the prognostic implications of TIL in resectable colorectal cancer liver metastases (CRCLM) have not been previously defined. This study examines the correlation between TIL numbers and survival following hepatic resection.

Methods

We studied patients who survived ≤2 or ≥10 years following CRCLM resection. Immunohistochemistry was performed on tissue microarrays (TMAs) to determine the number of T cells within CRCLM. Correlation between TIL frequency and ≤2 or ≥10 year survival was determined while controlling for established prognostic factors.

Results

Of 162 patients, 104 survived ≤2 years and 58 survived ≥10 years. Independent correlates of 10-year survival following CRCLM resection included a high number of CD8 T cells, a low number of CD4 T cells, and a clinical risk score of ≤2 (P < 0.001). Among 10-year survivors, 31% of patients had a high number of CD8 T cells compared with 8% for ≤2 year survivors (P < 0.01). Surprisingly, only 22% of 10-year survivors had a high number of CD4 T cells, in contrast to 69% of those who died within 2 years (P < 0.001). The combination of CD8 and CD4 T cell counts was a more powerful predictor of survival than either marker alone.

Conclusions

CRCLM T cell number is an independent correlate of long-term survival following liver resection. We conclude that CRCLM TIL analysis represents a potentially powerful prognostic tool which will require further validation prior to broad application.
Literature
1.
Choti MA, Sitzmann JV, Tiburi MF, et al. Trends in long-term survival following liver resection for hepatic colorectal metastases. Ann Surg. 2002;235(6):759–66.PubMedCrossRef
2.
Fong Y, Fortner J, Sun RL, et al. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg. 1999;230(3):309–18; discussion 318–21.PubMedCrossRef
3.
Tomlinson JS, Jarnagin WR, DeMatteo RP, et al. Actual 10-year survival after resection of colorectal liver metastases defines cure. J Clin Oncol. 2007;25(29):4575–80.PubMedCrossRef
4.
Falcone A, Ricci S, Brunetti I, et al. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol. 2007;25(13):1670–6.PubMedCrossRef
5.
Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350(23):2335–42.PubMedCrossRef
6.
Clemente CG, Mihm MC, Jr., Bufalino R, et al. Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma. Cancer. 1996;77(7):1303–10.PubMedCrossRef
7.
Fu J, Xu D, Liu Z, et al. Increased regulatory T cells correlate with CD8 T-cell impairment and poor survival in hepatocellular carcinoma patients. Gastroenterology. 2007;132(7):2328–39.PubMedCrossRef
8.
Galon J, Costes A, Sanchez-Cabo F, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006;313(5795):1960–4.PubMedCrossRef
9.
Pages F, Berger A, Camus M, et al. Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med. 2005;353(25):2654–66.PubMedCrossRef
10.
Zhang L, Conejo-Garcia JR, Katsaros D, et al. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med. 2003;348(3):203–13.PubMedCrossRef
11.
Hunder NN, Wallen H, Cao J, et al. Treatment of metastatic melanoma with autologous CD4 + T cells against NY-ESO-1. N Engl J Med. 2008;358(25):2698–703.PubMedCrossRef
12.
Wagner P, Koch M, Nummer D, et al. Detection and functional analysis of tumor infiltrating T-lymphocytes (TIL) in liver metastases from colorectal cancer. Ann Surg Oncol. 2008.
13.
Sasaki A, Tanaka F, Mimori K, et al. Prognostic value of tumor-infiltrating FOXP3 + regulatory T cells in patients with hepatocellular carcinoma. Eur J Surg Oncol. 2008;34(2):173–9.PubMed
14.
Katz SC, Pillarisetty VG, Bleier JI, et al. Conventional liver CD4 T cells are functionally distinct and suppressed by environmental factors. Hepatology. 2005;42(2):293–300.PubMedCrossRef
15.
Katz SC, Pillarisetty VG, Bleier JI, et al. Liver sinusoidal endothelial cells are insufficient to activate T cells. J Immunol. 2004;173(1):230–5.PubMed
16.
Kingham TP, Chaudhry UI, Plitas G, et al. Murine liver plasmacytoid dendritic cells become potent immunostimulatory cells after Flt-3 ligand expansion. Hepatology. 2007;45(2):445–54.PubMedCrossRef
17.
Pillarisetty VG, Shah AB, Miller G, et al. Liver dendritic cells are less immunogenic than spleen dendritic cells because of differences in subtype composition. J Immunol. 2004;172(2):1009–17.PubMed
18.
Bamboat ZM, Stableford JA, Plitas G, et al. Human liver dendritic cells promote T cell hyporesponsiveness. J Immunol. 2009;182(4):1901–11.PubMedCrossRef
19.
Goubier A, Dubois B, Gheit H, et al. Plasmacytoid dendritic cells mediate oral tolerance. Immunity. 2008;29(3):464–75.PubMedCrossRef
20.
Cohen T, Prus D, Shia J, et al. Expression of P53, P27 and KI-67 in colorectal cancer patients of various ethnic origins: clinical and tissue microarray based analysis. J Surg Oncol. 2008;97(5):416–22.PubMedCrossRef
21.
Hoos A, Cordon-Cardo C. Tissue microarray profiling of cancer specimens and cell lines: opportunities and limitations. Lab Invest. 2001;81(10):1331–8.PubMed
22.
Miller R, Siegmund D. Maximaly selected chi square statistics. Biometrics. 1982;38:1011–6.CrossRef
23.
Antony PA, Piccirillo CA, Akpinarli A, et al. CD8 + T cell immunity against a tumor/self-antigen is augmented by CD4 + T helper cells and hindered by naturally occurring T regulatory cells. J Immunol. 2005;174(5):2591–601.PubMed
24.
Hiraoka N, Onozato K, Kosuge T, et al. Prevalence of FOXP3 + regulatory T cells increases during the progression of pancreatic ductal adenocarcinoma and its premalignant lesions. Clin Cancer Res. 2006;12(18):5423–34.PubMedCrossRef
25.
Galon J, Fridman WH, Pages F. The adaptive immunologic microenvironment in colorectal cancer: a novel perspective. Cancer Res. 2007;67(5):1883–6.PubMedCrossRef
26.
Ostenstad B, Lea T, Schlichting E, et al. Human colorectal tumour infiltrating lymphocytes express activation markers and the CD45RO molecule, showing a primed population of lymphocytes in the tumour area. Gut. 1994;35(3):382–7.PubMedCrossRef
27.
Yu C, Yu HS, Sun KH, et al. Anti-CD45 isoform antibodies enhance phagocytosis and gene expression of IL-8 and TNF-alpha in human neutrophils by differential suppression on protein tyrosine phosphorylation and p56lck tyrosine kinase. Clin Exp Immunol. 2002;129(1):78–85.PubMedCrossRef
28.
Takayama E, Koike Y, Ohkawa T, et al. Functional and Vbeta repertoire characterization of human CD8 + T-cell subsets with natural killer cell markers, CD56 + CD57- T cells, CD56 + CD57 + T cells and CD56- CD57 + T cells. Immunology. 2003;108(2):211–9.PubMedCrossRef
29.
Cubas R, Li M, Chen C, et al. Colorectal cancer: new advances in immunotherapy. Cancer Biol Ther. 2007;6(1):11–7.PubMed
30.
Vermorken JB, Claessen AM, van Tinteren H, et al. Active specific immunotherapy for stage II and stage III human colon cancer: a randomised trial. Lancet. 1999;353(9150):345–50.PubMedCrossRef
31.
Rains N, Cannan RJ, Chen W, et al. Development of a dendritic cell (DC)-based vaccine for patients with advanced colorectal cancer. Hepatogastroenterology. 2001;48(38):347–51.PubMed
32.
Chong G, Bhatnagar A, Cunningham D, et al. Phase III trial of 5-fluorouracil and leucovorin plus either 3H1 anti-idiotype monoclonal antibody or placebo in patients with advanced colorectal cancer. Ann Oncol. 2006;17(3):437–42.PubMedCrossRef
33.
Posner MC, Niedzwiecki D, Venook AP, et al. A phase II prospective multi-institutional trial of adjuvant active specific immunotherapy following curative resection of colorectal cancer hepatic metastases: cancer and leukemia group B study 89903. Ann Surg Oncol. 2008;15(1):158–64.PubMedCrossRef
Metadata
Title
T Cell Infiltrate Predicts Long-Term Survival Following Resection of Colorectal Cancer Liver Metastases
Authors
Steven C. Katz, MD
Venu Pillarisetty, MD
Zubin M. Bamboat, MD
Jinru Shia, MD
Cyrus Hedvat, MD
Mithat Gonen, PhD
William Jarnagin, MD
Yuman Fong, MD
Leslie Blumgart, MD
Michael D’Angelica, MD
Ronald P. DeMatteo, MD
Publication date
01-09-2009
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 9/2009
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-009-0585-3

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