Clinical role of CD274 (PD-L1) and CD3+ lymphocytes in predicting high risk in advanced colorectal cancer patients receiving neoadjuvant chemotherapy.

Abstract

In cancer research, themechanism underlying theimmune response to atumour has been ofgreat interest. In this study, we investigated therole ofCD274 (programmed cell death-ligand 1 - PD-L1) and CD3+ tumour-infiltrating lymphocytes (TILs) in theprognosis ofadvanced colorectal cancer (CRC) patients treated with neoadjuvant chemotherapy. We retrospectively examined primary tumour specimens from stage III/IV CRC patients operated on between 2008 and 2018. We found asignificant association between these biomarkers and pT stage (PD-L1, p = 0.020; CD3+TILs, p = 0.025), tumour grade (PD-L1, p = 0.005; CD3+TILs, p = 0.004), positive surgical margin (PD-L1, p = 0.001; CD3+TILs, p = 0.001), MSI (PD-L1, p < 0.001; CD3+TILs, p < 0.001), etc. We also discovered that these biomarkers are independent risk factors for MSI (PD-L1, OR = 1.84 [1.27-4.02], p = 0.003; CD3+TILs, OR = 1.92 [1.31-4.35], p = 0.008). Univariate analysis results revealed that patients with high PD-L1, low CD3+TIL, and both showed poor relapse-free survival (RFS) and poor overall survival (OS) (PD-L1: RFS, p = 0.008 and OS, p = 0.001; CD3+TILs: RFS, p = 0.003 and OS, p = 0.005; PD-L1 and CD3+TILs: RFS, p < 0.001 and OS, p < 0.001). Theresults ofthemultivariate analysis showed that thecombined use ofhigh PD-L1 and low CD3+TILs was abetter predictor ofpoor RFS and OS (PD-L1 and CD3+TILs: RFS, hazard ratio - HR, = 2.85 [95% CI: 1.36-3.84], p < 0.001); OS, HR = 2.74 [1.32-3.71], p < 0.001). We also found ahigh PD-L1 parameter as another independent overall and relapse-free survival parameter. Our findings suggest that acombination ofhigh PD-L1 and low CD3+TIL can reliably predict poor survival in CRC patients receiving chemotherapy. Therefore, these biomarkers may be promising for theplanning and execution ofappropriate targeted therapies.