Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jun 3;15(1):67.
doi: 10.1186/s13000-020-00977-1.

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

Yun Liang  1 , Minghua Yu  2 , Caiyun Zhou  2 , Xiaojun Zhu  3
Affiliations

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

Yun Liang et al. Diagn Pathol. .

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.

Keywords: Cervix; Neoadjuvant chemotherapy; PD-L1; Squamous cell carcinoma; Tumor infiltrating lymphocytes.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Immunohistochemical staining patterns for PD-L1 on tumor cell. Representative negative expression (A), patchy expression (B), marginal(C), and diffuse expression(D) for PD-L1
Fig. 2
Fig. 2
Distribution of PD-L1 expression before and after NAC. More patients had PD-L1 expression with a threshold > 1% (A) and > 50% (B) after NAC
Fig. 3
Fig. 3
Immunohistochemical staining for TILs. CD3(A), CD8(B), and CD4(C) were present in both tumor area and surrounding peritumoral stroma
Fig. 4
Fig. 4
Survival analysis of cervical cancer patients. Kaplan-Meier curves for disease free survival of cervical cancer patients classified according to PD-L1 change (A) and PD-L1 expression after NAC (B)
See this image and copyright information in PMC

References

    1. Torre LA, Siegel RL, Ward EM, Jemal A. Global Cancer incidence and mortality rates and trends--an update. Cancer Epidemiol Biomark Prev. 2016;25(1):16–27. doi: 10.1158/1055-9965.EPI-15-0578. - DOI - PubMed
    1. Li L, Wu M, Ma S, Tan X, Zhong S. Neoadjuvant chemotherapy followed by radical hysterectomy for stage IB2-to-IIB cervical cancer: a retrospective cohort study. Int J Clin Oncol. 2019;24(11):1440–1448. doi: 10.1007/s10147-019-01510-1. - DOI - PubMed
    1. Borcoman E, Le Tourneau C. Pembrolizumab in cervical cancer: latest evidence and clinical usefulness. Ther Adv Med Oncol. 2017;9(6):431–439. doi: 10.1177/1758834017708742. - DOI - PMC - PubMed
    1. Dafni U, Tsourti Z, Vervita K, Peters S. Immune checkpoint inhibitors, alone or in combination with chemotherapy, as first-line treatment for advanced non-small cell lung cancer. A systematic review and network meta-analysis. Lung Cancer. 2019;134:127–140. doi: 10.1016/j.lungcan.2019.05.029. - DOI - PubMed
    1. Kim R, Keam B, Hahn S, Ock C-Y, Kim M, Kim TM, et al. First-line Pembrolizumab Versus Pembrolizumab Plus Chemotherapy Versus Chemotherapy Alone in Non-small-cell Lung Cancer: A Systematic Review and Network Meta-analysis. Clin Lung Cancer. 2019;20(5):331–8.e4. - PubMed

MeSH terms