title: Clinical significance of T cell clonality and expression levels of immune-related genes in endometrial cancer.
abstract: Immune microenvironment characterized by T cell clonality as well as expression signatures of immune-related genes in endometrial cancer tissues may play significant roles in clinical outcome of patients. We aimed to investigate the clinical significance of immune-related gene expression and TCR repertoire in endometrial cancer. Using total RNAs extracted from 32 endometrioid endometrial cancer cases, we performed quantitative real-time PCR to measure mRNA expression levels of immune-related genes including TRB, CD8, GZMA, HLA-A, CD11c and PD-L1. Higher mRNA expression levels of CD8 (P=0.039) and CD11c (P=0.046) in the 32 tissue samples were significantly associated with longer progression-free survival (PFS). Expression levels of CD8 (P<0.001) and CD11c (P=0.048) were also significantly associated with longer PFS in 540 cases in TCGA database. We also performed T cell receptor β (TCRβ) sequencing of tumor-infiltrating lymphocytes (TILs) on an Illumina MiSeq platform. To evaluate clonal expansion of TCRβ clonotypes, we adjusted the number of abundant TCRβ clonotypes by TRB mRNA expression levels and examined TCR clonality with the expression levels of immune-related genes and clinicopathological factors. The cases with high clonal T cell expansion along with high PD-L1 expression in cancer tissues was related to higher mRNA expression levels of CD8 (P<0.001), GZMA (P<0.001) and HLA-A (P=0.027), showed a significantly longer PFS (P=0.015), indicating a possibility that these parameters may serve as faborable prognostic factors. Considering clinical stage, mRNA expression of CD8 (P=0.037), GZMA (P=0.027) and HLA-A (P=0.022) was significantly higher in tumors at an early stage. Thus, we identified clinical and prognostic significance of immune microenvironment including the T cell clonality of TILs as well as PD-L1 and CD11c mRNA expression levels in endometrial cancer tissues.
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ikeda
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Kiyotani
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Poh Yin
authors.initials: PY
authors.lastname: Yew
authors.affiliation: Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Saitama 3501298, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Sato
authors.affiliation: Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Saitama 3501298, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Imai
authors.affiliation: Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 1088639, Japan.
authors.forename: Rui
authors.initials: R
authors.lastname: Yamaguchi
authors.affiliation: Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 1088639, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Miyano
authors.affiliation: Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Saitama 3501298, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fujiwara
authors.affiliation: Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Saitama 3501298, Japan.
authors.forename: Kosei
authors.initials: K
authors.lastname: Hasegawa
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D039521:CD11c Antigen / Q000235:genetics; D016827:CD8 Antigens / Q000235:genetics; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D053804:Granzymes / Q000235:genetics; D006801:Humans; D053208:Kaplan-Meier Estimate; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000473:pathology; D008875:Middle Aged; D011379:Prognosis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology
chemical_list: D014408:Biomarkers, Tumor; D039521:CD11c Antigen; D016827:CD8 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D053804:Granzymes; C509212:GZMA protein, human