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Assessment of the presence and anti-tumor potential of tumor-infiltrating lymphocytes in patients with acute myeloid leukemia

Authors Wei L, Wang Z, Zhang Z, Li Y, Fan S, Zhao Y, Liu Z, Ye X, Zhang F, Yu Y, Liu X, Cao F, Zhou J

Received 29 December 2018

Accepted for publication 18 March 2019

Published 12 April 2019 Volume 2019:11 Pages 3187—3196

DOI https://doi.org/10.2147/CMAR.S199817

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Andrew Yee

Peer reviewer comments 2

Editor who approved publication: Dr Alexandra R. Fernandes


Liya Wei,1 Zhenkun Wang,2 Zhuo Zhang,1 Yinghua Li,1 Shengjin Fan,1 Yanqiu Zhao,1 Zhiyu Liu,2 Xiangmei Ye,2 Fan Zhang,2 Yingying Yu,2 Xiaolong Liu,2 Fenglin Cao,2 Jin Zhou1,2

1Department of Hematology, The First Affiliated Clinical Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, People’s Republic of China; 2Central Laboratory of Hematology and Oncology, First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, People’s Republic of China

Purpose: Assessing the possibility of finding tumor-infiltrating lymphocytes (TIL) in bone marrow of acute myeloid leukemia (AML) patients and evaluating the anti-tumor activity of these TIL against autologous AML cells.
Patients and methods: TIL were immunomagnetically isolated by using anti-CD3 from bone marrow samples of 20 patients at the presentation of AML or four weeks upon completion of chemotherapy. TIL were ex vivo expanded for two weeks and immunophenotyped. Functionality in terms of cytokine secretion and cytotoxicity was assessed by γ-interferon quantitation and Elispot assay, respectively.
Results: TIL were detected in bone marrow samples of 50% (10/20) of the patient cohort. They were noted to highly express CD137 and PD-1 and display a significantly higher anti-tumor reactivity compared to that of autologous peripheral blood lymphocytes. TIL could be expanded in co-cultures with irradiated feeder cells supplemented with interleukin (IL)-7 and IL-15.
Conclusion: Data suggested the presence of reactive γ-interferon-secreting TIL in AML patients. They are expandable and possess anti-tumor activity, which might have a great potential in the development of adoptive cellular therapy for AML.

Keywords: tumor-infiltrating lymphocytes, acute myeloid leukemia, adoptive cell therapy, immunotherapy


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