Immunophenotyping with high-dimensional flow cytometry identifies Treg cell subsets associated with recurrence in papillary thyroid carcinoma

in Endocrine-Related Cancer
Authors:
Sijin Li Department of Thyroid Surgery, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China

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Zhen Chen Department of Thyroid Surgery, Guangzhou First People’s Hospital, Guangzhou, China

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Mengchu Liu School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, China

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Liang Li Medical Research Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China

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Wensong Cai Department of Thyroid Surgery, Guangzhou First People’s Hospital, Guangzhou, China

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Zhe-Xiong Lian Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China

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Haixia Guan Department of Endocrinology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China

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Bo Xu Department of Thyroid Surgery, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China

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https://orcid.org/0000-0003-2259-8245

Correspondence should be addressed to H Guan or B Xu: guanhaixia@gdph.org.cn or eyboxu@scut.edu.cn
DOI:
https://doi.org/10.1530/ERC-23-0240
Volume/Issue:
Volume 31: Issue 3
Article Type:
Research Article
Article ID:
e230240
Online Publication Date:
05 Feb 2024
Copyright:
© the author(s) 2024
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The activation of Treg cell subsets is critical for the prognosis of tumor patients; however, their heterogeneity and disease association in papillary thyroid carcinoma (PTC) need further investigation. We performed high-dimensional flow cytometry for immunophenotyping on thyroid tissues and matched peripheral blood samples from patients with multinodular goiters or PTC. We analyzed CD4+ T cell and Treg cell phenotypes and compared the recurrence-free survival of PTC patients with different Treg cell subset characteristics using TCGA. Furthermore, PTC recurrent and non-recurrent group were compared by multiplex immunohistochemistry. High-dimensional flow cytometry and bioinformatics analysis revealed an enrichment of Tregs in tumors compared with multinodular goiters and peripheral blood specimens. Moreover, effector Tregs (e-Tregs) as well as FOXP3+ non-Tregs were enriched in tumor samples, and the expression of CD39, PD-1, and CD103 increased on tumor Tregs. TCGA data analysis showed that individuals with CD39hi PD-1loCD103loe-Treghi and CD39loPD-1loCD103hie-Treghi expression patterns had a high recurrence rate. According to the multiplex immunohistochemistry and analysis, compared with non-recurrent group, the proportion of high recurrence rate effector Treg clusters (CD39+PD-1−CD103− plus CD39−PD-1−CD103+) was increased in recurrent patients. Overall, our results highlight the potential of e-Treg subsets as future immunotherapy targets for PTC recurrence.

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Print ISSN:
1351-0088
Online ISSN:
1479-6821
Copyright:
© the author(s) 2024
Article ID:
e230240
Received Date:
26 Jul 2023
Accepted Date:
12 Jan 2024
Print Publication Date:
01 Mar 2024
Online Publication Date:
05 Feb 2024
Keywords:
flow cytometry; papillary thyroid carcinoma; recurrence; Treg

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