Liver resection after neoadjuvant chemotherapy including bevacizumab offers the possibility of cure in patients with colorectal liver metastases. The clinical value of immune checkpoint expression as prognostic biomarker is unclear.
Expression analyses of IDO-1, PD-L1 and CTLA-4 were performed by immunohistochemistry in resected colorectal liver metastases in patients who underwent liver resection after neoadjuvant chemotherapy including bevacizumab (2005-2011). Association of expression of immune checkpoints in tumor cells and immune cells with response, RFS and OS was investigated.
One hundred forty-six patients were enrolled [88 (60.3%) male/58 (39.7%) female, median age 63.0 years (31.0-80.4)]. High expression of CTLA-4 in tumor cells was associated with shorter OS (median OS 48.2 months versus not reached, HR 2.04, P = 0.028). High expression of IDO-1 and PD-L1 in immune cells was associated with longer OS (not reached versus 47.1 months, HR 0.43, P = 0.016 and not reached versus 47.1 months, HR 0.41, P = 0.017). Results of IDO-1 remained significant in multivariable analysis (HR 0.29, P = 0.006). Low expression of CTLA-4 in tumor cells was associated with better histologic response (26 major, 19 partial, 18 none versus 14 major, 23 partial, 30 none, P = 0.032). No association of expression was found with RFS and radiologic response.
The clinical meaning of immune checkpoint expression and its association with response and survival were dependent on the expressing cell types. IDO-1 and CTLA-4 may be new prognostic and/or predictive biomarkers in patients with colorectal liver metastases. The role of immune checkpoint inhibitors in a multidisciplinary treatment approach remains to be elucidated.
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