Dataset Information

Variation of PD-L1 expression in locally advanced cervical cancer following neoadjuvant chemotherapy.

ABSTRACT:

Background

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.

Methods

A 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.

Results

The 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).

Conclusions

Cisplatin 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.

SUBMITTER: Liang Y

PROVIDER: S-EPMC7271386 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Publications

Variation of PD-L1 expression in locally advanced cervical cancer following neoadjuvant chemotherapy.

Liang Yun Y Yu Minghua M Zhou Caiyun C Zhu Xiaojun X

Diagnostic pathology 20200603 1

<h4>Background</h4>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.<h4>Methods</h4>A 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+ t ...[more]

PMID: 32493336

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Project description:Concurrent chemoradiotherapy is the standard treatment for locally advanced uterine cervical cancer. However, effective neoadjuvant chemotherapy (NAC) can reduce tumor size and facilitate hysterectomy for locally advanced uterine cervical cancer. NAC treatment could improve the prognosis of patients with locally advanced cervical cancer. However, if NAC is ineffective, radiotherapy must be pursued. This causes a delay in initiating the core treatment and results in a worse prognosis. Therefore, the identification of predictive markers of whether NAC is likely to be effective for the treatment of locally advanced uterine cervical cancer could improve patient prognosis. Uncoupling protein 2 (UCP2) is broadly expressed in cancer cells, and suppresses mitochondrial reactive oxygen species (ROS) production. UCP2 contributes to both carcinogenesis and chemoresistance by reducing ROS. Downregulation of UCP2 results in significantly increased cell death following chemotherapy. The present study investigated the association between UCP2 expression and NAC effectiveness. A total of 58 patients with locally advanced uterine cervical cancer (stage IIIA or IIIB) treated at Osaka City University Hospital between April 1995 and March 2010 were examined. Tumor tissue samples were obtained by punch biopsy prior to NAC. UCP2 expression was examined immunohistochemically and scored using a weighted scoring system. Patients were divided into NAC effective (n=34) and ineffective (n=24) groups. Furthermore, UCP2 expression in human uterine cervical cancer cells was inhibited by genipin, and changes in cisplatin sensitivity were examined. UCP2 weighted score was higher in the NAC ineffective group than in the NAC effective group (P=0.038). Additionally, the low UCP2 expression group was more sensitive to NAC than the high UCP2 expression group (P=0.041). Sensitivity to cisplatin was significantly increased when UCP2 was inhibited in human uterine cervical cancer cells in vitro. UCP2 expression may become a predictive marker of whether NAC is effective for patients with locally advanced uterine cervical cancer, which could improve patient prognosis.

Project description:BackgroundImmune checkpoint inhibitors (ICIs) have shown promising prospects in locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma (GC/GEJC) immunotherapy, but their efficacy in neoadjuvant settings remains unclear. This study aimed to assess the efficacy and safety of integrating programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors into neoadjuvant chemotherapy (NACT) of GC/GEJC treatment.MethodsPubMed, Cochrane Library, Embase, ClinicalTrials.gov, and main oncology conference databases were systematically searched up to 19 November 2022, and randomized controlled trials (RCTs) and cohort studies that evaluated the efficacy and safety of PD-1/PD-L1 inhibitors plus NACT were included. The main outcomes were pathological complete response (pCR), major pathological response (MPR), R0 resection rate, and treatment-related adverse events (TRAEs).ResultsA total of 753 patients from 20 prospective studies were included in this meta-analysis. The pooled pCR and MPR rates from studies reporting were 21.7% [95% confidence interval (CI), 18.1%-25.5%] and 44.0% (95% CI, 34.1%-53.8%), respectively. The pooled incidence rate of total TRAEs was 89.1% (95% CI, 82.7%-94.3%), and the incidence rate of grade 3 to 4 TRAEs was 34.4% (95% CI, 17.8%-66.5%). The pooled R0 resection rate was reported to be 98.9% (95% CI, 97.0%-99.9%). Subgroup analysis has not found significant differences in efficacy and safety among different PD-1/PD-L1 inhibitors. Moreover, the efficacy in patients with positive PD-L1 expression (combined positive score ≥1) was comparable with that in the entire study population [pCR, 22.5% vs. 21.2% (p > 0.05); MPR, 48.6% vs. 43.7% (p > 0.05)].ConclusionThis systematic review and meta-analysis found that PD-1/PD-L1 inhibitors combined with NACT for locally advanced GC/GEJC were well tolerated and may confer therapeutic advantages. The integration of ICIs into NACT has shown the potential for application in any PD-L1 expression population.

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Dataset Information

Variation of PD-L1 expression in locally advanced cervical cancer following neoadjuvant chemotherapy.

Background

Methods

Results

Conclusions

Publications

Variation of PD-L1 expression in locally advanced cervical cancer following neoadjuvant chemotherapy.

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