Correspondence

Immune Cells in Colorectal Cancer

N Engl J Med 2006; 354:1531-1532April 6, 2006

Article

To the Editor:

Pagès and coworkers (Dec. 22 issue)1 described the critical importance of the presence of CD45RO+ cells for prevention of early progressive disease in patients with colorectal cancer.

Most CD4+CD25+ regulatory T cells express CD45RO and are expanded in epithelial cancers.2 Therefore, we wonder why the authors did not comment on the role of CD4+CD25+ regulatory T cells in their patients. Our own data suggest that a high content of intratumoral CD4+CD25+ regulatory T cells in ovarian cancer is associated with a poor prognosis.3

Dominik Wolf, M.D.
Christian Marth, M.D., Ph.D.
Anna Maria Wolf, M.D.
Innsbruck Medical University, 6020 Innsbruck, Austria
dominik.wolf@uibk.ac.at

3 References

1. 1

   Pages F, Berger A, Camus M, et al. Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med 2005;353:2654-2666
   Full Text | Web of Science | Medline

2. 2

   Wolf AM, Wolf D, Steurer M, Gastl G, Gunsilius E, Grubeck-Loebenstein B. Increase of regulatory T cells in the peripheral blood of cancer patients. Clin Cancer Res 2003;9:606-612
   Web of Science | Medline

3. 3

   Marth C, Fiegl H, Zeimet AG, et al. Interferon-gamma expression is an independent prognostic factor in ovarian cancer. Am J Obstet Gynecol 2004;191:1598-1605
   CrossRef | Web of Science | Medline

Author/Editor Response

Regulatory T cells may play an important role in the host's antitumor immune response.1,2 Our data showed that the percentage of CD4+CD25+ T cells was increased among CD3+ cells in the group of tumors positive for the presence of vascular emboli, lymphatic invasion, and perineural invasion (collectively referred to as VELIPI), but no difference was found when this subpopulation was assessed as a percentage of the total cells. Expression levels of cytotoxic-T-lymphocyte–associated protein 4 and the glucocorticoid-induced tumor necrosis factor receptor and messenger RNA expression levels of interleukin-10 and transforming growth factor β (often associated with regulatory T cells) did not differ between patient groups.

We have also measured the regulatory T-cell transcription factor FOXP3 by polymerase chain reaction in 100 samples of colorectal carcinoma and found no increase in either group of patients. Moreover, the median survival of patients with tumors that had high expression of FOXP3 (48 patients) or low expression of FOXP3 (50 patients) was 35.5 and 36.0 months, respectively (P=0.50), and the median disease-free survival was 20 and 41 months, respectively (P=0.70).

These data did not support an obvious correlation among subpopulations of regulatory T cells, VELIPI status, and prognosis in colorectal cancer.

Franck Pagès, M.D., Ph.D.
Jérôme Galon, Ph.D.
INSERM Unité 255, 75006 Paris, France
jerome.galon@u255.bhdc.jussieu.fr

2 References

1. 1

   Curiel TJ, Coukos G, Zou L, et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 2004;10:942-949
   CrossRef | Web of Science | Medline

2. 2

   Dranoff G. The therapeutic implications of intratumoral regulatory T cells. Clin Cancer Res 2005;11:8226-8229
   CrossRef | Web of Science | Medline