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Prognostic significance of tumor-infiltrating lymphocytes and macrophages in nasopharyngeal carcinoma: a systematic review and meta-analysis

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Abstract

Purpose

Many studies have investigated the prognostic value of tumor-infiltrating lymphocytes (TILs) and tumor-infiltrating macrophages (TIMs) in patients with nasopharyngeal carcinoma (NPC), but the results remain controversial. Here, we performed a meta-analysis to evaluate the prognostic significance of TILs/TIMs in patients with NPC

Methods

The study was registered with PROSPERO (CRD42021234078). PubMed, Embase, and Web of Science databases were searched up to Dec 30, 2020. We reviewed studies that evaluated the relationship between TILs/TIMs and overall survival (OS), disease-free survival (DFS), or progression-free survival (PFS) in NPC. For TILs, CD3, CD4, CD8, and FOXP3 were searched as T-cell markers, CD19 and CD20 as B-cell markers, and CD56 as a natural killer cell marker. For TIMs, CD68 and CD163 were searched as total and M2 macrophage markers, respectively.

Results

In total, 19 studies with 3708 NPC were included in this meta-analysis. We found that high total numbers of TILs were significantly associated with favorable OS [hazard ratio (HR) 0.46, 95% confidence interval (CI) 0.38–0.57 and PFS (HR 0.48, 95% CI 0.38–0.62)]. In contrast, tumor infiltration by CD3+ T cells (HR 0.55, 95% CI 0.39–0.76), CD4+ T cells (HR 0.40, 95% CI 0.18–0.85), and CD8+ T cells (HR 0.56, 95% CI 0.34–0.93) correlated positively with OS. No significant relationship was found between survival and tumor infiltration by FOXP3+ T cells, CD68+ macrophages, or CD163+ macrophages.

Conclusion

Our findings revealed that tumor infiltration by CD3+ , CD4+ , and CD8+ T cells could be prognostic biomarkers in NPC.

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Availability of data and materials

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

NPC:

Nasopharyngeal carcinoma

TILs:

Tumor-infiltrating lymphocytes

TME:

Tumor microenvironment

TIMs:

Tumor-infiltrating macrophages

AJCC:

American Joint Committee on Cancer

CI:

Confidence interval

DFS:

Disease-free survival

HR:

Hazard ratio

OS:

Overall survival

PFS:

Progression-free survival

HNSCC:

Head and neck squamous cell carcinoma

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Acknowledgements

We thank Anne M. O’Rourke, PhD, from Liwen Bianji, Edanz Group China (www.liwenbianji.cn/ac), for editing the English text of a draft of this manuscript.

Funding

This work was supported by High-level Construction Project of Guangzhou Medical University and Upper Respiratory Disease Innovation and Transformation Platform Construction Project of Guangdong Provincial.

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Author notes

  1. Weixing Liu, Gui Chen, and Chunyi Zhang are first authors.

Authors and Affiliations

  1. State Key Laboratory of Respiratory Disease, Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiangxi Road, Guangzhou, 510120, China

    Weixing Liu, Gui Chen, Chunyi Zhang, Xiao Liao, Junyang Xie, Tianhao Liang, Wenjing Liao, Lijuan Song & Xiaowen Zhang

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  1. Weixing Liu
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Contributions

(1) WL, GC, CZ, and XZ: conception and design, (2) XZ: administrative support, (3) WL, GC, and CZ: provision of study materials or patients, (4) WL, GC, and XL: collection and assembly of data, (5) CZ, X, JX, TL, WL, and LS: data analysis and interpretation, (6) manuscript writing: all authors, and (7) final approval of manuscript: all authors.

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Correspondence to Xiaowen Zhang.

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Liu, W., Chen, G., Zhang, C. et al. Prognostic significance of tumor-infiltrating lymphocytes and macrophages in nasopharyngeal carcinoma: a systematic review and meta-analysis. Eur Arch Otorhinolaryngol 279, 25–35 (2022). https://doi.org/10.1007/s00405-021-06879-2

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