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.
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.
Authors: Dominik Pretscher; Luitpold V Distel; Gerhard G Grabenbauer; Michael Wittlinger; Maike Buettner; Gerald Niedobitek Journal: BMC Cancer Date: 2009-08-22 Impact factor: 4.430
Authors: Matthias Haas; Arno Dimmler; Werner Hohenberger; Gerhard G Grabenbauer; Gerald Niedobitek; Luitpold V Distel Journal: BMC Gastroenterol Date: 2009-09-04 Impact factor: 3.067