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Tumor-infiltrating cytotoxic T cells but not regulatory T cells predict outcome in anal squamous cell carcinoma.
Grabenbauer, Gerhard G; Lahmer, Godehard; Distel, Luitpold; Niedobitek, Gerald.
Afiliação
  • Grabenbauer GG; Department of Radiation Oncology, Friedrich Alexander University, Erlangen, Germany. gg@strahlen.imed.uni-erlangen.de
Clin Cancer Res ; 12(11 Pt 1): 3355-60, 2006 Jun 01.
Article em En | MEDLINE | ID: mdl-16740757
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.
Assuntos
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Bases de dados: MEDLINE Assunto principal: Neoplasias do Ânus / Carcinoma de Células Escamosas / Linfócitos T Citotóxicos / Linfócitos do Interstício Tumoral / Linfócitos T Reguladores Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Male / Middle aged Idioma: En Revista: Clin Cancer Res Assunto da revista: NEOPLASIAS Ano de publicação: 2006 Tipo de documento: Article País de afiliação: Alemanha
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Bases de dados: MEDLINE Assunto principal: Neoplasias do Ânus / Carcinoma de Células Escamosas / Linfócitos T Citotóxicos / Linfócitos do Interstício Tumoral / Linfócitos T Reguladores Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Male / Middle aged Idioma: En Revista: Clin Cancer Res Assunto da revista: NEOPLASIAS Ano de publicação: 2006 Tipo de documento: Article País de afiliação: Alemanha