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Tumor-Infiltrating Cytotoxic T Cells but not Regulatory T Cells Predict Outcome in Anal Squamous Cell Carcinoma

Authors' Affiliations: ¹ Department of Radiation Oncology and ² Institute for Pathology, Friedrich Alexander University, Erlangen, Germany

Requests for reprints: Gerhard G. Grabenbauer, Department of Radiation Oncology, University Hospital, Universitätsstr. 27, 91054 Erlangen, Germany. Phone: 49-9131-8534086; Fax: 49-9131-8534185; E-mail: gg{at}strahlen.imed.uni-erlangen.de.

Purpose: Tumor-infiltrating lymphocytes (TIL) are a possible prognostic factor in solid tumors. Cytotoxic TILs are generally considered as prognostically favorable, whereas regulatory T cells (Treg) may have adverse effects by virtue of their ability to inhibit effector cells. We have evaluated the effect of T-cell subsets on survival in patients with anal squamous cell carcinoma following radiochemotherapy.

Methods: Biopsy specimens from 38 patients with anal carcinomas were evaluated using tissue microarrays and immunohistochemistry for the presence of tumor-infiltrating immune cells using CD3, CD4, CD8, and CD68 antibodies. Treg were identified using an antibody directed against the transcription factor FoxP3, and granzyme B served as a marker for cytotoxic cells. Intratumoral immune cells were enumerated using a semiautomatic image analysis program. Prognostic effect of TIL subsets was evaluated by the log-rank test comparing no evidence of disease survival for groups with high and low numbers using median values as cutoff.

Results: CD3⁺ and CD4⁺ TILs influenced no evidence of disease survival: 3-year rates for patients with low numbers were 89% and 95%, respectively, and 54% (P = 0.02) and 48%, (P = 0.01), respectively, in cases with high numbers. Large numbers of tumor-infiltrating granzyme B⁺ cytotoxic cells had a significant negative prognostic effect (P = 0.008), whereas no effect was observed for Treg.

Conclusions: TILs were identified as negative prognostic indicators in anal squamous cell carcinomas with granzyme B⁺ cytotoxic cells showing highest effect on outcome. This is possibly explained by the selection of therapy-resistant tumor cell clones. No prognostic influence of Treg was found. Knowledge of local immune responses is important for the development of immunotherapeutic strategies.

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