Simultaneous disruption of circulating miR‐21 and cytotoxic T lymphocytes (CTLs): Prospective diagnostic and prognostic markers for esophageal squamous cell carcinoma (ESCC)

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) as the most prominent type of esophageal cancer (EC) in developing countries encompasses a substantial contribution of cancer‐related mortalities and morbidities. Cytotoxic T lymphocytes (CTLs) are the major subset of effector T cells against cancer. However, the microRNAs involved in the development and regulation of CTLs could be disrupted in cancers such as EC. METHODS: Here, we evaluated the population of IL‐10, TGF‐β, IFN‐γ, and IL‐17a‐producing CD3+CD8+ T cells, their association with the circulating levels of miR‐21 and miR‐29b, and their diagnostic and/or prognostic (after 160 weeks of follow‐up) utilities in 34 ESCC patients (12 newly diagnosed: ND, 24 under‐treatment: UT) and 34 matched healthy donors. RESULTS: The population of IL‐10 and TGF‐β‐producing CTLs (CD8+ Tregs) were considerably expanded, in addition to the overexpression of miR‐21 in both groups (ND and UT) of ESCC patients, while the frequency of Tc17 and CD8+ Treg cells increased only in UT patients. The expression means of TGF‐β and IL‐10 in CTLs were considered to be excellent biomarkers (1 ≥ area under the curve: AUC ≥0.9) in distinguishing ESCC patients and associated subgroups from healthy subjects. Moreover, the lower expressions of TGF‐β, IL‐17a, IL‐10, and IFN‐γ in CTLs were associated with ESCC better prognosis. CONCLUSIONS: The association between the impaired function of CD3+ CD8+ T cell subsets and miR‐21 expression could be introduced as novel therapeutic targets and powerful diagnostic and prognostic markers for ESCC.