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Abstract
BackgroundHigh Programmed death ligand 1 (PD-L1) expression are thought to be necessary to PD-1/PD-L1 axis blockades in many tumors. The aim of the study was to explore the variation of PD-L1 expression after neoadjuvant chemotherapy (NAC) in cervical squamous cell carcinoma (SCC) and its clinical implications.MethodsA total of 142 paired SCC specimens before and after platinum-based NAC were obtained from cervical cancer patients. The expression of PD-L1 and CD3+, CD4+, CD8+ tumor infiltrating lymphocytes (TILs) was detected by immunohistochemistry and the association between TILs, chemotherapy response, clinical outcome and PD-L1 expression was evaluated.ResultsThe fraction of patients with high PD-L1 expression was significantly increased from 32.4 to 46.5% after NAC (χ2 = 5.897, p = 0.015), while the increase of CD3+, CD4+, CD8+ TILs was not significant. High PD-L1 expression was not associated with CD3+, CD4+, CD8+ TILs before NAC, however CD8+ TILs infiltration was positively associated with high PD-L1 expression after NAC (r = 0.205, p = 0.014). The decreased PD-L1 expression was more observed in patients with clinical response to NAC (χ2 = 6.890, p = 0.009). A longer DFS was seen in patients with decreased PD-L1 expression than those with elevated or stable PD-L1 expression (p = 0.048, 95% CI: 0.091–0.987), while the difference was not significant in multivariate analysis (p = 0.113, 95% CI: 0.108–1.266).ConclusionsCisplatin based chemotherapy can increase PD-L1 expression in cervical cancer. The increased PD-L1 expression and a lymphocyte predominant microenvironment after chemotherapy provide a rational for use of PD-1/PD-L1 axis-inhibitor in the neoadjuvant setting.
Highlights
High Programmed death ligand 1 (PD-L1) expression are thought to be necessary to progressive disease (PD)-1/PD-L1 axis blockades in many tumors
We investigated the dynamics of PD-L1 expression and CD4, CD3, CD8+ tumor infiltrating lymphocytes (TILs) to ascertain whether cervical cancer patients could benefit from immunotherapy following primary treatment
In our patients before neoadjuvant chemotherapy (NAC), PD-L1 expression was observed coexistence with lymphocytes in some areas, no significant correlations between tumor PD-L1 expression and CD3+, CD4+, CD8+ TILs was seen, which implied that the influence of local immune response to PD-L1 expression is limited at this time
Summary
High Programmed death ligand 1 (PD-L1) expression are thought to be necessary to PD-1/PD-L1 axis blockades in many tumors. The aim of the study was to explore the variation of PD-L1 expression after neoadjuvant chemotherapy (NAC) in cervical squamous cell carcinoma (SCC) and its clinical implications. As one of the adjuvant treatments of cervical cancer, NAC reduces tumor volume, increases tumor resectability, and eliminates micro-metastases. Recent data suggested that tumor cell injury from chemotherapy can change the tumor microenvironment [6]. Not all the patients with high PD-L1 expression have response to immune checkpoint treatment and the degree of tumor infiltrating lymphocytes (TILs) in the tumor microenvironment are correlated with the clinical outcomes of anti-PD-1/PDL1 therapies [7]
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