The repertoire of tumor-infiltrating lymphocytes within the microenvironment of oral squamous cell carcinoma reveals immune dysfunction

  • Hongzhi QuanEmail author
  • Zhongyan Shan
  • Ziyi Liu
  • Sixuan Liu
  • Liu Yang
  • Xiaodan Fang
  • Kun Li
  • Baisheng Wang
  • Zhiyuan Deng
  • Yanjia Hu
  • Zhigang Yao
  • Junhui Huang
  • Jianjun Yu
  • Kun Xia
  • Zhangui Tang
  • Liangjuan FangEmail author
Original Article



The role of tumor-infiltrating lymphocytes (TILs) in the immune remodeling of tumor microenvironments (TME) in oral squamous cell carcinoma (OSCC) remains controversial. In this study, we pursued a comprehensive characterization of the repertoire of TILs and then analyzed its clinical significance and potential prognostic value.


Fresh tumor tissue samples and peripheral blood from 83 OSCC patients were collected to comprehensively characterize the phenotypes and frequencies of TILs by flow cytometry. Archived paraffin-embedded tissues derived from 159 OSCC patients were analyzed by immunohistochemistry to further assess the TIL repertoire. The clinical significance of TILs and their potential prognostic value were further analyzed.


A series of unique features of TILs were observed. IL-17 was highly expressed in betel nut chewers, and CD20 was abundantly expressed in patients who did not drink alcohol; high expression of CD138, PD-L1, and Foxp3 was associated with poor prognosis. The Th17/Treg ratio was an independent prognostic factor for patient survival with greater predictive accuracy for overall survival.


Our results suggest an antigen-driven immune response; however, the immune dysfunction within the microenvironment in OSCC and the Th17/Treg balance may play important roles in the modulation of antitumor immunity.


Tumor-infiltrating lymphocytes Immune microenvironment Oral squamous cell carcinoma Clinical significance Prognosis 



Area under curve


Regulatory B cells


Confidence interval


Head and neck squamous cell carcinoma


High-power fields.


Hazard ratios


Oral squamous cell carcinoma


Receiver operating characteristic


T cytotoxic 17


T-cell receptor β chain variable region


T helper 17


T-cell immunoglobulin and mucin-domain containing-3


Author contributions

Conception and design: HZQ, ZYS, and LJF; Data acquisition: ZYS, ZYL, SXL, LY, XDF, BSW, and KL; Evaluation of pathology and IHC: ZYD, YJH, JHH, and ZGY; Data analysis and interpretation: HZQ, ZYS, LJF, ZYL, LY, JJY, KX, and TZT; Writing and review of manuscript: HZQ, ZYS, LJF, and ZGT.


This work was supported by the National Natural Science Foundation of China (81501110), Hunan Province Natural Science Foundation (2016JJ4093), and China Postdoctoral Science Foundation (2016M592454).

Compliance with ethical standards

Conflict of interest

None of the authors report any conflict of interest.

Ethical approval

This work was approved by the Ethics Committee of Xiangya Stomatological Hospital and School of Stomatology under the Reference Number 2016003 and was conducted in accordance with the principles of the Declaration of Helsinki.

Informed consent

Written informed consent to the use of specimens and clinical data for research purposes was obtained from the patients of the flow cytometry cohort before recruitment into the study. For the IHC cohort, the patient also signed consent to the use of their specimens and clinical data for research purposes before surgical resection.

Supplementary material

262_2020_2479_MOESM1_ESM.pdf (280 kb)
Supplementary file1 (PDF 280 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2020

Authors and Affiliations

  • Hongzhi Quan
    • 1
    • 2
    Email author
  • Zhongyan Shan
    • 1
    • 2
  • Ziyi Liu
    • 1
    • 2
  • Sixuan Liu
    • 1
    • 2
  • Liu Yang
    • 1
    • 2
  • Xiaodan Fang
    • 1
    • 2
  • Kun Li
    • 1
    • 2
  • Baisheng Wang
    • 1
    • 2
  • Zhiyuan Deng
    • 1
    • 2
  • Yanjia Hu
    • 1
    • 2
  • Zhigang Yao
    • 1
    • 3
  • Junhui Huang
    • 1
    • 3
  • Jianjun Yu
    • 4
  • Kun Xia
    • 5
  • Zhangui Tang
    • 1
    • 2
  • Liangjuan Fang
    • 6
    • 7
    Email author
  1. 1.Research Institution of Stomatology, Xiangya Stomatological Hospital and School of StomatologyCentral South UniversityChangshaPeople’s Republic of China
  2. 2.Department of Oral Maxillofacial Surgery, Xiangya Stomatological Hospital and School of StomatologyCentral South UniversityChangshaPeople’s Republic of China
  3. 3.Department of Oral Pathology, Xiangya Stomatological Hospital and School of StomatologyCentral South UniversityChangshaPeople’s Republic of China
  4. 4.Department of Head and Neck Surgery, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangshaPeople’s Republic of China
  5. 5.Center for Medical Genetics, School of Life ScienceCentral South UniversityChangshaPeople’s Republic of China
  6. 6.Department of Neurology, Xiangya HospitalCentral South UniversityChangshaPeople’s Republic of China
  7. 7.Key Laboratory of Hunan Province in Neurodegenerative DisordersCentral South UniversityChangshaPeople’s Republic of China

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