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Open Access 01-08-2021 | Colorectal Cancer | Original Article

CD30⁺OX40⁺ Treg is associated with improved overall survival in colorectal cancer

Authors: Jian Hang Lam, Michelle Hong, Si-Lin Koo, Clarinda Wei Ling Chua, Kah Ling Lim, Felicia Wee, Wei Keat Wan, Wei Qiang Leow, Joo Guan Yeo, Iain Bee Huat Tan, Joe Yeong, Tony Kiat Hon Lim, Tong Seng Lim

Published in: Cancer Immunology, Immunotherapy | Issue 8/2021

Abstract

Regulatory T cells (Tregs) are often enriched in tumors, where their immunosuppressive function has a key role in tumor persistence and progression. In colorectal cancer (CRC), however, Tregs are frequently associated with an improved clinical outcome. Tumor-infiltrating Tregs have been shown to exhibit a distinct signature comprising the co-stimulatory molecules (OX40, 4-1BB), cytokine receptors (IL1R2, IL21R, CCR8, CD30), and co-inhibitory molecules (PD-L1, TIGIT). Here, we showed by flow cytometry that circulating CD45RO⁺ Tregs from patients with CRC (n = 25) have elevated CD30 and OX40 expression compared to healthy subjects (n = 14). We identified co-expression of CD30 and OX40 on circulating CD45RO⁺ Tregs using single-cell images captured by the DEPArray^™ system. The frequency of CD30⁺OX40⁺CD45RO⁺ Tregs was significantly higher in CRC patients than in healthy subjects (P < 0.001). Importantly, receiver operating characteristic analysis confirmed that this CD30⁺OX40⁺ Treg subset could strongly discriminate between CRC patients and healthy subjects with the highest accuracy of 92.3%, an AUC of 0.92, a sensitivity of 88%, a specificity of 100%, a positive predictive value of 100%, a negative predictive value of 82.35%, and a trade-off value of 3.44%, compared to other Treg subsets. Consistently, multiplex-IHC/IF of tumor-infiltrating Tregs revealed a significant association between high densities of CD30⁺OX40⁺ Tregs and improved overall survival; no such association was found for other subsets. These data suggest a potential role for CD30⁺OX40⁺ Tregs as a diagnostic or prognostic biomarker in CRC.

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Title: CD30+OX40+ Treg is associated with improved overall survival in colorectal cancer
Authors: Jian Hang Lam
Michelle Hong
Si-Lin Koo
Clarinda Wei Ling Chua
Kah Ling Lim
Felicia Wee
Wei Keat Wan
Wei Qiang Leow
Joo Guan Yeo
Iain Bee Huat Tan
Joe Yeong
Tony Kiat Hon Lim
Tong Seng Lim
Publication date: 01-08-2021
Publisher: Springer Berlin Heidelberg
Keywords: Colorectal Cancer
Colorectal Cancer
Published in: Cancer Immunology, Immunotherapy / Issue 8/2021
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-021-02859-x

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