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

• Published in: Clinical cancer research 2006-06, Vol.12 (11), p.3355-3360
• Main Authors: Grabenbauer, Gerhard G, Lahmer, Godehard, Distel, Luitpold, Niedobitek, Gerald
• Format: Article
• Language: English
• Subjects: anal cancer; Anus Neoplasms - diagnosis; Anus Neoplasms - immunology; Anus Neoplasms - radiotherapy; Carcinoma, Squamous Cell - diagnosis; Carcinoma, Squamous Cell - immunology; Carcinoma, Squamous Cell - radiotherapy; cytotoxic T cells; Female; Follow-Up Studies; Gastrointestinal cancers: colorectal; Humans; Lymphocytes, Tumor-Infiltrating - immunology; Male; Middle Aged; Predictive Value of Tests; Prognosis; regulatory T cells; Survival Rate; T cells; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Regulatory - immunology; Treatment Outcome; Tumor Immunobiology; Tumor microenvironment and modification
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-05-2434

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.