The repertoire of tumor-infiltrating lymphocytes within the microenvironment of oral squamous cell carcinoma reveals immune dysfunction
- 81 Downloads
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.
KeywordsTumor-infiltrating lymphocytes Immune microenvironment Oral squamous cell carcinoma Clinical significance Prognosis
Area under curve
Regulatory B cells
Head and neck squamous cell carcinoma
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
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.
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.
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.
- 3.Beynon RA, Lang S, Schimansky S et al (2018) Tobacco smoking and alcohol drinking at diagnosis of head and neck cancer and all-cause mortality: results from head and neck 5000, a prospective observational cohort of people with head and neck cancer. Int J Cancer 143:1114–1127. https://doi.org/10.1002/ijc.31416 CrossRefPubMedPubMedCentralGoogle Scholar
- 12.Balermpas P, Rödel F, Rödel C et al (2015) CD8+ tumour-infiltrating lymphocytes in relation to HPV status and clinical outcome in patients with head and neck cancer after postoperative chemoradiotherapy: a multicentre study of the German cancer consortium radiation oncology group (DKTK-ROG). Int J Cancer 138:171–181CrossRefGoogle Scholar
- 16.Doescher J, Veit JA, Hoffmann TK (2017) The 8th edition of the AJCC cancer staging manual. HNO 1–5Google Scholar
- 30.Chen J, He Q, Liu J, Xiao Y, Xiao C, Chen K, Xie D, Zhang X (2018) CD8+ tumor-infiltrating lymphocytes as a novel prognostic biomarker in lung sarcomatoid carcinoma, a rare subtype of lung cancer. Cancer Manag Res 10:3505–3511. https://doi.org/10.2147/CMAR.S169074 CrossRefPubMedPubMedCentralGoogle Scholar
- 35.Wolf GT, Chepeha DB, Bellile E, Nguyen A, Thomas D, McHugh J, University of Michigan H, Neck SP (2015) Tumor infiltrating lymphocytes (TIL) and prognosis in oral cavity squamous carcinoma: a preliminary study. Oral Oncol 51:90–95. https://doi.org/10.1016/j.oraloncology.2014.09.006 CrossRefGoogle Scholar
- 43.Sfanos KS, Bruno TC, Maris CH, Xu L, Thoburn CJ, DeMarzo AM, Meeker AK, Isaacs WB, Drake CG (2008) Phenotypic analysis of prostate-infiltrating lymphocytes reveals TH17 and Treg skewing. Clin Cancer Res 14:3254–3261. https://doi.org/10.1158/1078-0432.CCR-07-5164 CrossRefPubMedPubMedCentralGoogle Scholar
- 51.Taghavi N, Mohsenifar Z, Baghban AA, Arjomandkhah A (2018) CD20+ Tumor infiltrating B lymphocyte in oral squamous cell carcinoma: correlation with clinicopathologic characteristics and heat shock protein 70 expression. Pathol Res Int 2018:4810751. https://doi.org/10.1155/2018/4810751 CrossRefGoogle Scholar