Prognostic value of tumour-infiltrating CD8+ lymphocytes in rectal cancer after neoadjuvant chemoradiation: is indoleamine-2,3-dioxygenase (IDO1) a friend or foe?

Abstract

The prognostic value of the local immune phenotype in patients with colorectal cancer has been extensively studied. Neoadjuvant radiotherapy and/or chemotherapy may potentially influence these immune responses. In this study, we examined the prognostic role of indoleamine-2,3-Dioxygenase (IDO1) and infiltrating cytotoxic T lymphocytes (CD8+) in locally advanced rectal carcinomas after neoadjuvant treatment. Expression of IDO1 and CD8 was evaluated by immunohistochemistry in 106 archival tumour tissue samples from patients following neoadjuvant chemoradiation and radical resection. The average infiltration of IDO1+ and CD8+ cells was calculated along the tumour invasive front, in the tumour centre and within the neoplastic cells and expressed as total scores. Of the tumour specimens evaluable for immunohistochemistry, 100% showed CD8+ lymphocyte infiltration and 93.4% stained positive for IDO1. Total IDO1 score positively correlated with total CD8 score for all three subsites (p = 0.002, Kendall-tau-b 0.357). A high total CD8 score was positively correlated with lower ypUICC-stages (p = 0.047) and lower ypT-categories (p = 0.032). Total IDO1 expression showed a clear trend towards a lower risk of recurrence (p = 0.078). A high total IDO1 score was an independent prognostic marker for prolonged disease-free survival (HR 0.38, p = 0.046) and a high total CD8 score for favourable overall survival (HR 0.16, p = 0.029). Analysis of the local CD8 and IDO1 expression profile may be a helpful tool in predicting prognosis for patients with locally advanced rectal cancer following neoadjuvant chemoradiation.