Tumour infiltrating lymphocyte expression of PD-1 as a favourable prognostic factor in patients with mismatch repair competent colorectal cancer.

Abstract

631 Background: Immune checkpoint activation is recognised in mismatch repair (MMR) deficient colorectal cancer (CRC), and Programmed Cell Death Protein-1 (PD-1) inhibitors have been shown to have therapeutic benefit in this patient group. However, the role of PD-1 and PD Ligand-1 (PDL-1) in patients with MMR competent CRC remains unclear. The present study examined the relationship between tumor infiltrating lymphocyte (TIL) PD-1 and tumour PDL-1 expression, tumour microenvironment (TME) characteristics and cancer-specific survival (CSS) of patients with MMR competent CRC. Methods: The presence of TIL PD-1 and tumour cell PDL-1 expression was examined in patients who had undergone resection of TNM I-III CRC using a tissue microarray. Relationship with clinicopathological characteristics and the TME (Klintrup-Makinen (KM) grade, Immunoscore, tumour stroma percentage (TSP) and Glasgow Microenvironment Score (GMS)) and CSS was examined. Results: 189 patients were included; 64% were older than 65 and 52% were male. PDL-1 expression was not associated with clinicopathological or TME characteristics. Lymphocyte PD-1 expression was not associated with clinicopathological characteristics, but was associated with a high KM grade ( P< 0.001), high Immunoscore ( P< 0.001), low TSP ( P= 0.068) and a low GMS ( P< 0.001). On multivariate survival analysis, high TIL PD-1 expression was associated with improved CSS (HR 0.60, P= 0.016) independent of Immunoscore (HR 0.74, P= 0.03) and TSP (HR 1.91, P= 0.027). PDL1 expression was not associated with CSS on univariate or multivariate analysis. Pre-operative aspirin use was known for 131 patients. Aspirin use showed a trend towards improved 5-year CSS in patients with low PDL-1 expression (100% vs. 77%, P= 0.103) but worse 5-year CSS in those with high expression (55% vs. 82%, P= 0.045). Conclusions: The presence of PD-1 expressing TILs is a favourable prognostic factor in MMR competent CRC independent of other TME characteristics. Furthermore, the relationship between aspirin and CSS may be dependent on PDL-1 expression. Both PD-1 and PDL-1 may be potential prognostic and predictive markers in patients with MMR competent CRC.