![]() In addition, the roughly linear decrease of TCR diversity with aging was confirmed using high-throughput sequencing technology, and the TCR repertoire diversity was correlated with the percentage of naïve T cells. Especially, reduced TCR diversity was observed in multiple tumor patients. The constriction of the TCR repertoire could cause impaired immune response to viral and bacterial infections, poor reaction to vaccination, and delayed immune recovery after chemotherapy and hematopoietic stem cell transplantation. The peripheral blood includes a substantial repertoire of T lymphocytes that gain the ability to recognize various antigens. In recent years, the application of deep sequencing technology has allowed for the quantitative analysis of the frequencies of distinct TCR clonotypes, providing precise measurement of TCR diversity. The CDR3 sequences have been viewed as the natural identifier of T cell clonality. The antigenic specificity of T lymphocytes is primarily determined by the sequences in the hypervariable CDR3 (complementarity-determining region 3) of the TCR. As many as 10 11 different TCRs can be generated during the somatic recombination process in human T cells. Moreover, nucleotide deletion or insertion at gene junction sites contributes to the substantial TCR diversity. The diversity of immune repertoires is created via recombination of variable (V), diversity (D), and joining (J) gene segments, which form the antigen-binding variable region. In addition, the genome-wide expression alterations confirmed the effects of decitabine on immune reconstitution, and the increase of TCR excision circles (TRECs) was validated.Ĭonclusions: The low-dose DNMT inhibitor decitabine broadens the peripheral T cell repertoire, providing a novel role for the epigenetic modifying agent in anti-tumor immune enhancement.ī and T lymphocytes possess the capacity to recognize foreign molecules through various antigen-binding receptors (B cell receptor and T cell receptor ). Further analysis showed a tendency for CD4 T cells with an increased CD4/CD8 ratio in response to decitabine therapy. Results: An increase of the unique productive sequences of the CDR3 of TCRβ was observed in all of the 4 patients after decitabine treatment, which was characterized by a lower abundance of expanded clones and increased TCR diversity compared with before decitabine treatment. We collected the peripheral blood mononuclear cells (PBMCs) from 4 patients, at baseline and after 2 cycles of low-dose decitabine therapy. We aimed to investigate the immunomodulatory effect of decitabine in peripheral T cells.Įxperimental design: We applied next-generation sequencing to investigate the complementarity-determining region 3 (CDR3) of the TCRβ gene, the diversity of which acts as the prerequisite for the host immune system to recognize the universal foreign antigens. Purpose: Decitabine, a promising epi-immunotherapeutic agent has shown clinical responses in solid tumor patients, while the anti-tumor mechanisms were unclear. Received: DecemAccepted: ApPublished: May 13, 2016 ![]() Keywords: T cell receptor repertoire, pharmacometabonomics, decitabine, epigenetic therapy, solid tumor ![]() Jing Nie 1, Yan Zhang 2, Xiang Li 1, Meixia Chen 2, Chuanjie Liu 1, Weidong Han 1, 2ġDepartment of Immunology, Institute of Basic Medical Science, PLA General Hospital, Beijing, 100853, ChinaĢDepartment of Biological Therapy, PLA General Hospital, Beijing, 100853, China
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