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 Nov 12:12:11585-11596.
doi: 10.2147/CMAR.S274913. eCollection 2020.

PD-L1 Expression is Highly Associated with Tumor-Associated Macrophage Infiltration in Nasopharyngeal Carcinoma

Rui Deng #  1 , Juan Lu #  1 , Xiong Liu  1 , Xiao-Hong Peng  1 , Jie Wang  1 , Xiang-Ping Li  1
Affiliations

PD-L1 Expression is Highly Associated with Tumor-Associated Macrophage Infiltration in Nasopharyngeal Carcinoma

Rui Deng et al. Cancer Manag Res. .

Abstract

Purpose: Tumour-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment and provide a barrier against the cytotoxic effector functions of T cells and natural killer (NK) cells. Recently, TAMs have become increasingly recognised as an attractive target in combination therapy with PD-1/PD-L1 immuno-checkpoint blockades (ICBs). However, the relationship between PD-L1 expression and TAMs remains unknown in nasopharyngeal carcinoma (NPC).

Patients and methods: A total of 212 NPC patients from Nanfang hospital were collected in this study. We evaluated the expression of PD-L1 in tumor cells, CD68 (pan-macrophages), and CD163 (M2-like macrophage) in NPC tissues using immunohistochemical (IHC) staining.

Results: The positivity of PD-L1 on tumor cells was 61.3% (130/212). The infiltration densities of CD68+ cells and CD163+ cells in PD-L1-positive NPC tissues were significantly higher than those in PD-L1-negative NPC tissues (P=0.0012 for CD68; P<0.0001 for CD163). Logistic regression analysis showed that high densities of CD68+ macrophages and CD163+ TAMs were significantly associated with increased PD-L1 expression. Subgroup analyses demonstrated that a positive PD-L1 expression on tumor cells in combination with lower CD163+ TAMs density was significantly associated with favorable prognosis, whereas negative PD-L1 expression on tumor cells with higher CD163+ TAMs density was associated with worse prognosis.

Conclusion: The PD-L1 expression in tumor cells was positively correlated with TAMs density in tumor microenvironment of NPC, suggesting TAMs as a new target for combination therapy to improve the response rate of ICBs in NPC treatment.

Keywords: PD-L1; nasopharyngeal carcinoma; prognosis; tumor microenvironment; tumor-associated macrophage.

PubMed Disclaimer

Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Immunohistochemistry staining of PD-L1, CD68 and CD163 expression in NPC tissues. The left panel (A) showed PD-L1 negative staining and low macrophage density. The right panel (B) showed positive PD-L1 staining and high macrophage density.
Figure 2
Figure 2
The relationships between PD-L1 expression in tumor cells and infiltration of CD68+ and CD163+ macrophages. (A) The distribution of PD-L1 expression in NPC cells and CD68+ macrophages. (B) The distribution of PD-L1 expression in NPC cells and CD163+ TAM.
Figure 3
Figure 3
The predictive accuracy of CD163+ TAMs and CD68+ macrophages on PD-L1 expression in NPC tissue samples.
Figure 4
Figure 4
Kaplan–Meier curves of OS and PFS in NPC patients based on PD-L1 expression in tumor cells (A, B), CD68 expression (C, D) and CD163 expression (E, F).
Figure 5
Figure 5
Kaplan–Meier analysis of PFA (A) and OS (B) in the 4 subgroups classified by PD-L1 expression on tumor cells and CD163+ TAMs density.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Zou X, You R, Liu H, et al. Establishment and validation of M1 stage subdivisions for de novo metastatic nasopharyngeal carcinoma to better predict prognosis and guide treatment. Eur J Cancer. 2017;77:117–126. doi:10.1016/j.ejca.2017.02.029 - DOI - PubMed
    1. Chen YP, Chan ATC, Le QT, Blanchard P, Sun Y, Ma J. Nasopharyngeal carcinoma. Lancet. 2019;394(10192):64–80. doi:10.1016/S0140-6736(19)30956-0 - DOI - PubMed
    1. Tan T, Lim WT, Fong KW, et al. Concurrent chemo-radiation with or without induction gemcitabine, carboplatin, and paclitaxel: a randomized, Phase 2/3 trial in locally advanced nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2015;91(5):952–960. doi:10.1016/j.ijrobp.2015.01.002 - DOI - PubMed
    1. Hsu JM, Li CW, Lai YJ, Hung MC. Posttranslational modifications of PD-L1 and their applications in cancer therapy. Cancer Res. 2018;78(22):6349–6353. doi:10.1158/0008-5472.CAN-18-1892 - DOI - PMC - PubMed
    1. Fang W, Yang Y, Ma Y, et al. Camrelizumab (SHR-1210) alone or in combination with gemcitabine plus cisplatin for nasopharyngeal carcinoma: results from two single-arm, Phase 1 trials. Lancet Oncol. 2018;19(10):1338–1350. doi:10.1016/S1470-2045(18)30495-9 - DOI - PubMed