ABSTRACT
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-ß, 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-ß-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-ß 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-ß, 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.
Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , MicroRNAs/blood , T-Lymphocytes, Cytotoxic/metabolism , Biomarkers, Tumor/blood , Biomarkers, Tumor/genetics , Cytokines/blood , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/genetics , Esophageal Neoplasms/metabolism , Esophageal Squamous Cell Carcinoma/diagnosis , Esophageal Squamous Cell Carcinoma/genetics , Esophageal Squamous Cell Carcinoma/metabolism , Humans , PrognosisABSTRACT
Defect in T lymphocyte homeostasis could implicate initiation and development of rheumatoid arthritis (RA). Since PD-1 plays a key role in the regulation of T lymphocytes, its expression pattern in various CD8+ T cell subsets could be so effective in RA pathogenesis. Here, we investigated the expression of PD-1 and CXCR3 on CD8+CD28- T cells in association with the IFN-γ levels in patients with RA. A total of 42 RA patients, including 10 newly-diagnosed (ND) and 32 relapsed (RL) cases and also 20 healthy donors were enrolled. Phenotypic characterization of CD8+ T cells derived from peripheral blood (PB) and synovial fluid (SF) was performed by flow cytometry. The plasma and SF IFN-γ levels were also assessed by ELISA. The frequency of CD8+CD28- T cells showed no significant differences between patients and controls while its higher levels were observed in PB, versus SF of RL patients. Relapsed patients also showed higher CXCR3 and especially PD-1 expression on their CD8+CD28- T cells. The IFN-γ concentration was elevated in SF of ND patients while its plasma level was significantly lower in RL subgroup than controls. Although PD-1 could induce immune suppression in effector T cells, it is upregulated during inflammation and its overexpression on CD8+CD28- T cells within inflammatory synovium is associated with severity of disease in our cohort of RA patients.
Subject(s)
Arthritis, Rheumatoid/metabolism , CD28 Antigens/metabolism , CD8-Positive T-Lymphocytes/metabolism , Programmed Cell Death 1 Receptor/metabolism , Synovial Membrane/metabolism , Synovitis/metabolism , Adult , Aged , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/immunology , Biomarkers/metabolism , CD8-Positive T-Lymphocytes/immunology , Case-Control Studies , Female , Humans , Interferon-gamma/metabolism , Male , Middle Aged , Phenotype , Prognosis , Receptors, CXCR3/metabolism , Recurrence , Synovial Membrane/immunology , Synovitis/diagnosis , Synovitis/immunologyABSTRACT
Dysregulation of helper T (Th) cell subsets has been contributed to the initiation and propagation of esophageal squamous cell carcinoma (ESCC). Different microRNAs (miRNAs) have been reported to control the development and functions of tumor-associated immune cells in ESCC. Here, we aimed to assess the IL-10, TGF-ß, IFN-γ, and IL-17a-producing CD3+CD8- T cells in association whit miR-21, miR-29b, miR-106a, and miR-155 expression in ESCC patients. A total of 34 ESCC patients including 12 newly diagnosed (ND) and 22 under-treatment (UT) cases and also 34 age-matched healthy donors were enrolled. Flow cytometric characterization of stimulated T cells was performed by staining of the cells with fluorescent conjugated specific anti-human CD3 and CD8 cell surface markers as well as IL-17a, IFN-γ, IL-10, and TGF-ß intracytoplasmic cytokines. Circulating RNA was extracted from the plasma, and qRT-PCR was used to evaluate the expression of microRNAs. TGF-ß plasma levels were also assessed by ELISA. Results showed that the frequency of Th cells was significantly reduced in patients. A significant increase in Treg as well as Th17 cells population in both patient subgroups was observed. ND patients showed elevated level of Th1 cells and IL-10. However the mean expression of IFN-γ was significantly decreased in Th cells. We also detected higher level of miR-21 in the ESCC patients which was significantly correlated with different subsets of Th cells. Our findings revealed that immune response related to the Th cells is highly impaired in ESCC patients. Association between miR-21 and Th subsets could be correlated with the impairment of anti-tumor immunity and ESCC pathogenesis, which could be potentially used as an important target for immunotherapeutic approaches.
