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CD45RA−Foxp3high regulatory T cells have a negative impact on the clinical outcome of head and neck squamous cell carcinoma

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Abstract

Background

Although regulatory T cells (Tregs) are thought to play an important role in immune suppression, their clinical significance in head and neck squamous cell carcinoma (HNSCC) is unclear. A recent study reported Tregs could be divided into functional subsets based on the expression of CD45RA and Foxp3.

Method

The frequency of circulating Treg subsets was analyzed in patients with HNSCC and compared with the frequency in patients with benign tumors. The association of Treg subsets with the frequency of lymphocyte subsets, status of progression, clinical course, and prognosis were also examined.

Results

The frequency of CD4+Foxp3+ Tregs was comparable between HNSCC patients and age-matched benign tumor patients; however, CD45RA−Foxp3high Tregs were significantly increased in HNSCC patients, in particular those with advanced stage tumors. The high frequency of CD45RA−Foxp3high Tregs correlated with a poor prognosis and the low frequency of CD45RA−Foxp3high Tregs before treatment showed a better clinical outcome, even in patients with advanced stage tumors. CD45RA−Foxp3high Treg numbers were decreased after intensive treatments; however, Treg numbers recovered in the early stages of recurrent cases, even before the clinical manifestation.

Conclusion

CD45RA−Foxp3high Tregs are associated with the clinical course of HNSCC and might be a new target for treatment and an early marker of tumor recurrence in HNSCC patients.

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Abbreviations

CDDP:

Cisplatin

CCRT:

Combined chemotherapy and radiotherapy

CFSE:

Carboxyfluorescein diacetate succinimidyl ester

CR:

Complete remission

CTLA-4:

Cytotoxic T-lymphocyte-associated protein 4

HNSCC:

Head and neck squamous cell carcinoma

MDSCs:

Myeloid derived suppressor cells

PBMCs:

Peripheral blood mononuclear cells

RT:

Radiation therapy

Tregs:

Regulatory T cells

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Acknowledgements

This study was funded by a Grants-in-Aid for Scientific Research from MEXT KAKENHI (Ministry of Education, Culture, Sports, Science and Technology) Grant number 15K10799.

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Author notes

  1. Fumie Ihara and Daiju Sakurai contributed equally to this study.

Authors and Affiliations

  1. Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan

    Fumie Ihara, Daiju Sakurai, Atsushi Horinaka, Yuji Makita, Akira Fujikawa, Toshioki Sakurai, Kazuki Yamasaki, Naoki Kunii & Yoshitaka Okamoto

  2. Department of Medical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan

    Fumie Ihara & Shinichiro Motohashi

  3. Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan

    Toshinori Nakayama

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  1. Fumie Ihara
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Correspondence to Yoshitaka Okamoto.

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Ihara, F., Sakurai, D., Horinaka, A. et al. CD45RA−Foxp3high regulatory T cells have a negative impact on the clinical outcome of head and neck squamous cell carcinoma. Cancer Immunol Immunother 66, 1275–1285 (2017). https://doi.org/10.1007/s00262-017-2021-z

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