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Clinical significance of CD38 and CD101 expression in PD-1+CD8+ T cells in patients with epithelial ovarian cancer.

ABSTRACT: Previous studies using mouse liver tumor models have indicated that coexpression of CD38 and CD101 in programmed cell death-1 (PD-1)+CD8+ T cells may reflect fixed dysregulation of CD8+ T cells and thus indicate a poor response to anti-PD-1 immunotherapy. However, whether CD38 and CD101 expression in PD-1+CD8+ T cells can predict the clinical status and efficacy of chemotherapy for various cancer types, including ovarian cancer (OC), remains unclear. In the present study, peripheral blood mononuclear cells (PBMCs) were obtained by Ficoll-Hypaque gradient centrifugation from 96 fresh samples from healthy adult volunteers and patients with epithelial OC, aged 55.21±9.91 years. Additionally, tumor-infiltrating lymphocytes (TILs) were separated using a combination of mechanical, chemical and enzymatic digestion from fresh surgically removed tumor tissues from 15 patients with epithelial OC. The expression of CD38 and CD101 in PD-1+CD8+ T cells or TILs was detected by flow cytometry or immunofluorescence (IF) staining, respectively. The association between the level of CD38/CD101 expression and clinicopathological parameters or postoperative chemotherapy in patients with OC was statistically analyzed. The levels of CD38/CD101-coexpressing PD-1+CD8+ T cells were significantly increased in PBMCs and TILs of patients with OC compared with those of healthy volunteers. The frequency of PD-1+CD38+CD101+CD8+ T cells among the total PD-1+CD8+ T cell subpopulation was negatively associated with clinical stage, lymph node metastasis and postoperative chemotherapy prognosis in patients with OC. Furthermore, IF staining confirmed colocalization of CD38 and CD101 on the majority of TILs in OC tissues. Thus, the present study suggests that coexpression of CD38 and CD101 in peripheral PD-1+CD8+ T cells and TILs may serve as a new indicator for diagnosis and treatment efficacy in patients with epithelial OC.

SUBMITTER: Zhou J

PROVIDER: S-EPMC7285834 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Clinical significance of CD38 and CD101 expression in PD-1+CD8+ T cells in patients with epithelial ovarian cancer.

Zhou Jian J Wang Wenting W Liang Zhiqing Z Ni Bing B He Wei W Wang Dan D

Oncology letters 20200428 1

Previous studies using mouse liver tumor models have indicated that coexpression of CD38 and CD101 in programmed cell death-1 (PD-1)+CD8+ T cells may reflect fixed dysregulation of CD8+ T cells and thus indicate a poor response to anti-PD-1 immunotherapy. However, whether CD38 and CD101 expression in PD-1+CD8+ T cells can predict the clinical status and efficacy of chemotherapy for various cancer types, including ovarian cancer (OC), remains ...[more]

PMID: 32565998

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Project description:ObjectiveEpithelial ovarian cancer (EOC) is a heterogeneous disease with diverse clinicopathological features and behaviors, and its heterogeneity may be concerned with the accumulation of multiple somatic oncogenic mutations. The major goals of this study are to systematically perform the comprehensive mutational profiling in EOC patients, and investigate the associations between somatic mutations and clinicopathological characteristics.MethodsA total of 80 surgical specimens were obtained from EOC patients who had previously undergone primary debulking surgery, and genomic DNAs were extracted from fresh-frozen tissues. We investigated mutational status in hot spot regions of 50 cancer-related genes by targeted next-generation sequencing using an Ion AmpliSeq Cancer Hotspot Panel v2 Kit.ResultsValidated mutations were detected in 66 of the 80 tumors (82.5%). The five most frequently mutated genes were TP53 (43.8%), PIK3CA (27.5%), KRAS (23.8%), PTEN (10%) and CTNNB1 (10%). PTEN and CTNNB1 mutations were associated with younger age. PIK3CA1, KRAS and CTNNB1 mutations were observed in early-stage, whereas TP53 mutations were more common in advanced stage. Significant associations were observed between TP53 mutation and serous carcinoma, and between KRAS mutation and mucinous carcinoma. Both PIK3CA mutation and CTNNB1 mutation were also significantly associated with endometrioid and clear cell carcinoma. The patients with PIK3CA and KRAS mutations were significantly associated with favorable progression free survival (PFS). In particular, PIK3CA mutations had more significant associations with favorable PFS than PIK3CA wild-type in the endometrioid subtype (P = 0.012). Patients with mutations only in TP53 were significantly associated with worse PFS.ConclusionEOCs were heterogeneous at the genomic level and harbored somatic oncogenic mutations. Our molecular profiling may have the potential for becoming a novel stratification within histological subtypes of EOC. Further studies are needed to define molecular classification for improved clinical outcomes and treatment of EOC patients in future.

Project description:The expression and clinical significance of stomatin-like protein 2 (SLP-2) in ovarian tumors were investigated. A total of 280 cases of ovarian tissue specimens preserved from inpatients after surgical treatments in the Department of Oncology of Yidu Central Hospital of Weifang from April 2013 to May 2016 were collected, including 130 cases of malignant ovarian tumor tissue specimens (malignant tumor group), 75 cases of benign ovarian tumor tissue specimens (benign tumor group) and 75 cases of normal ovarian tissue specimens from bilateral ovariectomy for unilateral ovarian lesions (control group). Immunohistochemistry was used to detect the expression of SLP-2 protein in the three groups. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was utilized to detect the relative expression of SLP-2 mRNA in the three groups, and the relationship between SLP-2 and clinicopathological parameters of the ovarian cancer patients was analyzed. The patients with ovarian cancer were divided into the SLP-2 high-expression group and the SLP-2 low-expression group according to the median of SLP-2 relative expression. The survival of patients was analyzed using the Kaplan-Meier and Cox regression model. The results of immunohistochemistry showed that the positive expression rate of SLP-2 protein in the malignant tumor group was significantly higher than that in the benign tumor and control groups (P<0.001). The results of RT-qPCR showed that compared with the control group, the relative expression of SLP-2 mRNA in the ovarian tissues in the benign tumor group and the malignant tumor group was increased (P<0.001). The relative expression of SLP-2 mRNA in the malignant tumor group was higher than that in the benign tumor group (P<0.001). The relative expression of SLP-2 mRNA correlated with clinical stage, pathological differentiation and lymph node metastasis of the patients with ovarian cancer (P<0.05). The 5-year overall survival (OS) in the SLP-2 mRNA high expression group was significantly lower than that in the SLP-2 mRNA low expression group at 5 years (P<0.05). SLP-2 mRNA was an independent prognostic factor influencing OS of the patients (P<0.05). SLP-2 may be involved in the occurrence and development of ovarian cancer and related to the clinical stage, pathological differentiation and lymph node metastasis of the patients with ovarian cancer, which may also play a role in promoting the invasion and metastasis processes of ovarian cancer. Therefore, SLP-2 is expected to be an effective biomarker for targeted treatment and prognosis of ovarian tumor.

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Dataset Information

Clinical significance of CD38 and CD101 expression in PD-1+CD8+ T cells in patients with epithelial ovarian cancer.

Publications

Clinical significance of CD38 and CD101 expression in PD-1<sup>+</sup>CD8<sup>+</sup> T cells in patients with epithelial ovarian cancer.

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