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CD30 + OX40 + Treg is associated with improved overall survival in colorectal cancer.
- Source :
-
Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2021 Aug; Vol. 70 (8), pp. 2353-2365. Date of Electronic Publication: 2021 Feb 02. - Publication Year :
- 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 <superscript>+</superscript> 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 <superscript>+</superscript> Tregs using single-cell images captured by the DEPArray <superscript>™</superscript> system. The frequency of CD30 <superscript>+</superscript> OX40 <superscript>+</superscript> CD45RO <superscript>+</superscript> Tregs was significantly higher in CRC patients than in healthy subjects (P < 0.001). Importantly, receiver operating characteristic analysis confirmed that this CD30 <superscript>+</superscript> OX40 <superscript>+</superscript> 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 <superscript>+</superscript> OX40 <superscript>+</superscript> Tregs and improved overall survival; no such association was found for other subsets. These data suggest a potential role for CD30 <superscript>+</superscript> OX40 <superscript>+</superscript> Tregs as a diagnostic or prognostic biomarker in CRC.<br /> (© 2021. The Author(s).)
- Subjects :
- Biomarkers, Tumor immunology
Cells, Cultured
Humans
Leukocyte Common Antigens immunology
Prospective Studies
Receptors, Cytokine immunology
Retrospective Studies
Colorectal Neoplasms immunology
Colorectal Neoplasms mortality
Ki-1 Antigen immunology
Receptors, OX40 immunology
T-Lymphocytes, Regulatory immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1432-0851
- Volume :
- 70
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Cancer immunology, immunotherapy : CII
- Publication Type :
- Academic Journal
- Accession number :
- 33527196
- Full Text :
- https://doi.org/10.1007/s00262-021-02859-x