Endocrine Abstracts

In recent years, it was demonstrated that tumor infiltrating and circulating regulatory and cytotoxic T-cells are associated with clinical outcome in several solid tumors. However, their role in adrenocortical carcinoma (ACC) was never studied, although 60% of these tumors secrete autonomously cortisol, a well-established potent immunosuppressant that most likely influences the balance between different T-cells.

Firstly, we analyzed the circulating regulatory T cells (T(reg); CD4+CD25highFOXP3+) in 173 blood samples of ACC patients (44 tumor-free, 86 with tumor but no endogenous cortisol excess and 43 with present cortisol excess) compared to 20 healthy blood donors. Secondly, we performed immunofluorescence analyses on paraffin embedded primary tumor tissue from 58 ACC patients for T(reg)(CD3+FOXP3+), cytotoxic T lymphocytes (CTL; CD3+CD8+) and T-helper cells (CD3+CD4+). Furthermore, we performed uni- and multivariate survival analyses.

The percentage of circulating T(reg) in ACC patients with cortisol oversecretion was significantly higher than in the other ACC groups (7.7±4.5 vs. 5.7±3 and 5.5±2.5%; P<0.05) and much higher than in healthy donors (3.6±0.9%; P<0.001). While univariate analysis showed a significantly negative association of T(reg) with survival (HR=1.78; P=0.02), this influence disappeared in a multivariate analysis adjusting for tumor burden and cortisol excess.

In 41(70%) of ACC samples CTL tumor infiltrates were present (mean 17.8±46.1 cells/HPF) and 31 samples (64.5%) showed T(reg) infiltrates. However, no significant correlation with survival could be demonstrated in a multivariate analysis. Surprisingly, infiltrating CD4+T-cells, present in 17(35.4%) of cases, were independently associated with a better survival (HR=0.39(95%CI 0.16–0.91); P=0.03).

In conclusion, neither circulating T(reg) cells nor tumor infiltrating T(reg) nor CTL are associated with clinical outcome in patients with ACC after adjusting for tumor burden and cortisol secretion. Interestingly, CD4+T-cell infiltrates were significantly associated with a better prognosis suggesting a potentially relevant role of these cells in ACC.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details unavailable.