Clonal expansion of bone marrow CD8+ T cells in acute myeloid leukemia patients at new diagnosis and after chemotherapy.

Abstract

CD8+ T cells are crucial adaptive immune effectors and express receptors (T cell receptors, TCRs) that specifically recognize and eradicate tumor cells. The diversity of the TCR repertoire is generated by specialized genetic diversification mechanisms, which lead to an extremely variable TCR repertoire that is capable of recognizing a wide range of antigens. However, the variations in CD8+ TCR diversity and their clinical implications in acute myeloid leukemia (AML) patients remain unknown. CD8+ T cells were enriched from 10 healthy donors and 31 AML patients at diagnosis and after chemotherapy, and TCRβ deep sequencing was performed to analyze CD8+ T cell clonal expansion and TCR repertoire diversity. Diminished TCR repertoire diversity and increased T cell clone expansion were noted in the bone marrow of AML patients. In relapsed patients, T cells were found to be more clonally expanded after chemotherapy than at new diagnosis. Moreover, significantly more expanded TCRβ clonotypes were noted in CD8+ PD-1+ T cells than in CD8+ PD-1- T cells regardless of the time of examination. Our systematic T cell repertoire analysis may help better characterize CD8+ T cells before and after chemotherapy in AML, which may provide insights into therapeutic strategies for hematological malignancies.

• Authors: Zhongxin Feng, Qin Fang, Xingyi Kuang, Xin Liu, Ying Chen, Dan Ma, Jishi Wang
• Journal: American journal of cancer research (Am J Cancer Res) Vol. 10 Issue 11 Pg. 3973-3989 ( 2020) ISSN: 2156-6976 [Print] United States
• PMID: 33294280 (Publication Type: Journal Article)
• Copyright: AJCR Copyright © 2020.