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The expression and prognostic impact of proinflammatory cytokines and their associations with carcinogens in oropharyngeal squamous cell carcinoma

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Abstract

In oropharyngeal squamous cell carcinoma (OPSCC), the relationships between immune responses, carcinogens, and prognoses are not clarified yet. Here, we retrospectively reviewed the pathology samples of 46 OPSCC patients, and used p16 to determine their human papillomavirus (HPV) status. The Cancer Genome Atlas (TCGA) database was also analyzed for further comparison. The immunofluorescence staining of proinflammatory cytokines showed that high interferon gamma (IFNγ; T helper 1; Th1), low interleukin 4 (IL4; T helper 2; Th2), low thymic stromal lymphopoietin (TSLP; Th2), and low transforming growth factor beta (TGFβ; T regulatory; Treg) expressions were good prognostic factors for OPSCC. p16-positive OPSCC showed higher Th1, lower Th2/Treg proinflammatory cytokine expressions, and a better prognosis than p16-negative OPSCC. In smokers alone, although p16-positive OPSCC smokers showed weaker Th2/Treg predominant cytokine expressions than p16-negative OPSCC smokers, the prognoses of both groups were equally poor. As for p16-positive OPSCC patients alone, p16-positive nonsmokers showed a significantly better prognosis than p16-positive smokers, but the immune responses of both groups were all weakly Th2/Treg predominant. Overall, higher Th1 and lower Th2/Treg proinflammatory cytokine expressions are associated with a better prognosis for OPSCC. HPV may be related to increased Th1, decreased Th2/Treg responses, and a good prognosis, while smoking may be related to increased Th2/Treg, decreased Th1 responses, and a poor prognosis in OPSCC. The impact of smoking on immune deviation may be weaker than that of HPV, but the impact of smoking on prognosis may be stronger than that of HPV in OPSCC.

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Abbreviations

CCL22:

C-C motif chemokine ligand 22

CXCL10:

C-X-C motif chemokine ligand 10

R:

Correlation coefficient

DAB:

Diaminobenzidine tetrachloride

FFPE:

Formalin-fixed, paraffin-embedded

HNC:

Head and neck cancer

HR:

Hazard ratio

IF:

Immunofluorescence

OPSCC:

Oropharyngeal squamous cell carcinoma

PBST:

Phosphate-buffered saline with Tween 20

ROC:

Receiver-operating characteristic

TCGA:

The Cancer Genome Atlas

TSLP:

Thymic stromal lymphopoietin

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Acknowledgements

The authors thank Chao-jung Chang, Chien-Hua Wu, Hong-Jing Chuang, Yi-Chuan Lee, Chiao-Lun Lan, Yao-Te Chung, and Ying-Yin Chen for their technical assistance, thank Fang-Yu Tsai and Shih Sheng Jiang in Taiwan Bioinformatics Institute Core Facility (National Core Facility Program for Biotechnology, 107–2319-B400-001) for TCGA database analysis, and thank the First Common Laboratory of National Taiwan University Hospital, Yun-Lin Branch for providing the experimental platform.

Funding

This study was financially supported by a project from National Taiwan University Hospital, Yun-Lin Branch (Grant Number NTUHYL107.C036).

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Authors and Affiliations

  1. Department of Otolaryngology, National Taiwan University Hospital, Yun-Lin Branch, Yun-Lin, Taiwan

    Chi-Maw Lin

  2. Department of Pathology, National Taiwan University Hospital, Yun-Lin Branch, Yun-Lin, Taiwan

    Long-Wei Lin

  3. National Institute of Cancer Research, National Health Research Institutes, Miao-Li, Taiwan

    Ya-Wen Chen

  4. Department of Biotechnology, National Formosa University, Yun-Lin, Taiwan

    Chi-Maw Lin & Yi-Ling Ye

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  1. Chi-Maw Lin
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Contributions

Conceived and designed the research: C-ML and Y-LY. Collected the data: C-ML and L-WL. Reviewed the pathologic slide: L-WL. Analyzed the data: C-ML, Y-WC and Y-LY. Wrote and edited the paper: C-ML, Y-WC and Y-LY. Whole correspondence: Y-LY.

Corresponding author

Correspondence to Yi-Ling Ye.

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The authors declare that they have no conflict of interest.

Ethical approval and ethical standards

The Research Ethics Committee of the National Taiwan University hospital approved this study (NTUH IRB- 201711065RINC). All methods were performed in accordance with the Declaration of Helsinki.

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Written informed consent was waived by the ethics committee which approved this study.

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Lin, CM., Lin, LW., Chen, YW. et al. The expression and prognostic impact of proinflammatory cytokines and their associations with carcinogens in oropharyngeal squamous cell carcinoma. Cancer Immunol Immunother 69, 549–558 (2020). https://doi.org/10.1007/s00262-020-02488-w

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  • DOI: https://doi.org/10.1007/s00262-020-02488-w

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