Expression of PD-L1 in cervical carcinoma and its impact on survival associated with T-cell infiltration and FoxP3 expression

Abstract

Background: The PD-1/PD-L1 signaling axis is currently the most elucidated mechanism for tumor evasion of T-cell-mediated immunity. Nevertheless, few data are available regarding its impact on cervical cancer and the relationship with lymphocytic infiltrates. Methods: A retrospective assessment of all cases of cervical neoplasia treated in Caxias do Sul General Hospital, Brazil, between 2012 and 2016 was performed. Clinical and pathological data were collected from electronic records and analyzed. Original slides were independently reviewed by three pathologists to confirm diagnoses and to assess the immunohistochemical expression of PD-L1 and FoxP3 in tumor cells and lymphocytic infiltrates. Results: PD-L1 staining was present in 32.2% of the 59 cervical samples. Median overall survival time of the PD-L1-negative group was 47.8 months, a time point not yet reached by the PD-L1-positive group (p=0.968). Median progression-free survival was 24.3 months for PD-L1-negative and 11.5 months for PD-L1-positive patients (p=0.263). PD-L1 staining was found in 27.1% of the lymphocytic infiltrates, and survival analysis revealed no difference between PD-L1-positive and PD-L1-negative samples. There was no impact on survival related to FoxP3 staining in neither tumor samples nor lymphocytic infiltrates. Conclusion: Although the median progression-free survival times differed, the difference was not statistically significant. Our study corroborates the rationale that PD-L1 expression in cervical neoplasms has no impact on survival. PD-L1 expression in peritumoral lymphocytes revealed no impact on infiltration volume nor survival. Keywords: uterine cervical neoplasms, tumor-infiltrating lymphocytes, cancer, tumor microenvironment, survival.

Figure 1

Flowchart of cohort recruitment.

Figure 2

Immunohistochemical staining of PD-L1 was considered positive if cell membrane staining was detected, and FoxP3 staining was considered positive if nuclear staining was detected. Black arrows point to staining detection areas. PD-L1-positive squamous cell cervical neoplasia (A); 400× magnification. PD-L1-positive peritumoral inflammatory infiltrate (B); 400× magnification. FoxP3-positive squamous cell cervical neoplasia (C); 200× magnification. FoxP3-positive peritumoral inflammatory infiltrate (D; 400× magnification).

Figure 3

Kaplan–Meier curves and log-rank test analysis of the overall survival of patients with cervical neoplasia based on PD-L1 expression.

Figure 4

Kaplan–Meier curves and log-rank test analysis of the progression-free survival of patients with cervical neoplasia based on PD-L1 expression.

Figure 5

Kaplan–Meier curves and log-rank test analysis of overall survival (left) and progression-free survival (right) of patients with cervical neoplasia based on quantification of peritumoral lymphocytic infiltration.