Tumor-infiltrating cytotoxic T cells but not regulatory T cells predict outcome in anal squamous cell carcinoma.
OBJECTIVE
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.
Grabenbauer
Gerhard G
GG
Department of Radiation Oncology, Friedrich Alexander University, Erlangen, Germany. gg@strahlen.imed.uni-erlangen.de
Lahmer
Godehard
G
Distel
Luitpold
L
Niedobitek
Gerald
G
D001005:Anus Neoplasms / Q000175:diagnosis* / Q000276:immunology / Q000532:radiotherapy; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000276:immunology / Q000532:radiotherapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016896:Treatment Outcome