Abstract
The clinical value of immune checkpoint expression as prognostic biomarker in bevacizumab-pretreated patients with resected microsatellite-stable (MMS) colorectal liver metastases is unclear and was retrospectively investigated in this study. Expression analyses of IDO-1, PD-L1, and CTLA-4 were performed by immunohistochemistry in resected bevacizumab-pretreated colorectal liver metastases. Association of immune checkpoint expression in tumor cells and immune cells with response and clinical outcome was investigated. Expression profiles were compared with those of patients with anti-EGFR-targeted therapy and lung metastases, respectively. One hundred thirty-six patients with MMS disease were investigated (79 (58.1%) male/57 (41.9%) female, median age 62.9 years (range 31.0-80.4)). High expression of IDO-1 in immune cells was associated with longer OS (not reached versus 44.8 months, HR 0.23 (95% CI 0.09, 0.55), P=0.001). Low expression of CTLA-4 in tumor cells was associated with better histological response (26 major, 19 partial, 18 none versus 14 major, 23 partial, 30 none, P=0.032). Expression profiles differed compared to patients with anti-EGFR-targeted therapy and patients with lung metastases. Immune checkpoint expression was associated with response and survival. IDO-1 may serve as a novel prognostic and/or predictive biomarker in patients with MMS colorectal liver metastases.
Highlights
Liver resection is the gold standard in patients with colorectal liver metastases and offers the possibility of cure and long-term survival.[1]
This study shows for the first time that the expression of clinically relevant immune checkpoints in immune cells and tumor cells is associated with histological response and clinical outcome in patients with liver-limited, resectable MSS colorectal liver metastases who underwent neoadjuvant bevacizumab-based chemotherapy and liver resection in curative intent
We found a significantly different expression profile in patients who underwent anti-EGFR-based chemotherapy and in patients with resected lung metastases. These findings suggest that IDO-1 expression may serve as a novel predictive and/or prognostic biomarker in these patients in a treatment- and site-dependent matter
Summary
Liver resection is the gold standard in patients with colorectal liver metastases and offers the possibility of cure and long-term survival.[1] Perioperative chemotherapy has shown to be beneficial and the addition of bevacizumab is associated with high radiological and histological response rates.[2,3,4] predictive and prognostic biomarkers for the treatment with bevacizumab in patients with metastatic colorectal cancer are urgently needed Immune checkpoints such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and the programmed cell death protein 1(PD-1)/programmed death-ligand 1 (PD-L1) axis inhibit the anti-tumoral response of the patient’s immune system, and antibodies targeting these checkpoints have been introduced into clinical practice in various cancer entities.[5,6,7]. IDO-1 may serve as a novel prognostic and/or predictive biomarker in patients with MMS colorectal liver metastases
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