ORIGINAL ARTICLE
Clinical role of CD274 (PD-L1) and CD3+ lymphocytes in predicting high risk in advanced colorectal cancer patients receiving neoadjuvant chemotherapy
1
Department of General Surgery, Tekirdağ University, Tekirdağ, Turkey
2
Department of Pathology, Ankara Training and Research Hospital, Ankara, Turkey
Submission date: 2023-03-18
Final revision date: 2023-06-17
Acceptance date: 2023-06-21
Publication date: 2023-07-17
Corresponding author
Suat Benek
Assistant Professor Suat Benek Department of General Surgery Tekirdağ University Tekirdağ, Turkey
Assistant Professor Suat Benek Department of General Surgery Tekirdağ University Tekirdağ, Turkey
Pol J Pathol 2023;74(2):98-108
KEYWORDS
TOPICS
ABSTRACT
In cancer research, the mechanism underlying the immune response to a tumour has been of great interest. In this study, we investigated the role of CD274 (programmed cell death-ligand 1 – PD-L1) and CD3+ tumour-infiltrating lymphocytes (TILs) in the prognosis of advanced 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 a significant 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). The results of the multivariate analysis showed that the combined use of high PD-L1 and low CD3+TILs was a better predictor of poor 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 a high PD-L1 parameter as another independent overall and relapse-free survival parameter.
Our findings suggest that a combination of high PD-L1 and low CD3+TIL can reliably predict poor survival in CRC patients receiving chemotherapy. Therefore, these biomarkers may be promising for the planning and execution of appropriate targeted therapies.
We retrospectively examined primary tumour specimens from stage III/IV CRC patients operated on between 2008 and 2018.
We found a significant 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). The results of the multivariate analysis showed that the combined use of high PD-L1 and low CD3+TILs was a better predictor of poor 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 a high PD-L1 parameter as another independent overall and relapse-free survival parameter.
Our findings suggest that a combination of high PD-L1 and low CD3+TIL can reliably predict poor survival in CRC patients receiving chemotherapy. Therefore, these biomarkers may be promising for the planning and execution of appropriate targeted therapies.
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