The roles of stem cell memory T cells in hematological malignancies

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Abstract

Adoptive cell therapy (ACT) is rapidly migrating from bench to clinical therapy for hematological malignancies. Recently, a new subtype of memory T cells, stem cell memory T (T _SCM) cells, was shown to be one of the most favorable subsets for ACT. T _SCM has high self-renewal capacity and is associated with superior T cell engraftment, persistence, and antitumor immunity. In this review, we focused on the characteristics of antigen-specific T _SCM cells and discussed their potential for immunotherapy targeting hematological malignancies.

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IL-7 and IL-15 instruct the generation of human memory stem T cells from naive precursors.

Nicoletta Cieri, Barbara Camisa, Fabienne Cocchiarella … (2013)

Long-living memory stem T cells (T(SCM)) with the ability to self-renew and the plasticity to differentiate into potent effectors could be valuable weapons in adoptive T-cell therapy against cancer. Nonetheless, procedures to specifically target this T-cell population remain elusive. Here, we show that it is possible to differentiate in vitro, expand, and gene modify in clinically compliant conditions CD8(+) T(SCM) lymphocytes starting from naive precursors. Requirements for the generation of this T-cell subset, described as CD62L(+)CCR7(+)CD45RA(+)CD45R0(+)IL-7Rα(+)CD95(+), are CD3/CD28 engagement and culture with IL-7 and IL-15. Accordingly, T(SCM) accumulates early after hematopoietic stem cell transplantation. The gene expression signature and functional phenotype define this population as a distinct memory T-lymphocyte subset, intermediate between naive and central memory cells. When transplanted in immunodeficient mice, gene-modified naive-derived T(SCM) prove superior to other memory lymphocytes for the ability to expand and differentiate into effectors able to mediate a potent xenogeneic GVHD. Furthermore, gene-modified T(SCM) are the only T-cell subset able to expand and mediate GVHD on serial transplantation, suggesting self-renewal capacity in a clinically relevant setting. These findings provide novel insights into the origin and requirements for T(SCM) generation and pave the way for their clinical rapid exploitation in adoptive cell therapy.

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Superior T memory stem cell persistence supports long-lived T cell memory.

Jason Brenchley, Kaimei Song, Nichole Klatt … (2013)

Long-lived memory T cells are able to persist in the host in the absence of antigen; however, the mechanism by which they are maintained is not well understood. Recently, a subset of human T cells, stem cell memory T cells (TSCM cells), was shown to be self-renewing and multipotent, thereby providing a potential reservoir for T cell memory throughout life. However, their in vivo dynamics and homeostasis still remain to be defined due to the lack of suitable animal models. We identified T cells with a TSCM phenotype and stem cell-like properties in nonhuman primates. These cells were the least-differentiated memory subset, were functionally distinct from conventional memory cells, and served as precursors of central memory. Antigen-specific TSCM cells preferentially localized to LNs and were virtually absent from mucosal surfaces. They were generated in the acute phase of viral infection, preferentially survived in comparison with all other memory cells following elimination of antigen, and stably persisted for the long term. Thus, one mechanism for maintenance of long-term T cell memory derives from the unique homeostatic properties of TSCM cells. Vaccination strategies designed to elicit durable cellular immunity should target the generation of TSCM cells.

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The role of PD-1 and PD-L1 in T-cell immune suppression in patients with hematological malignancies

Li-Li Shi, Shaohua Chen, Lijian Yang … (2013)

T-cell activation and dysfunction relies on direct and modulated receptors. Based on their functional outcome, co-signaling molecules can be divided as co-stimulators and co-inhibitors, which positively and negatively control the priming, growth, differentiation and functional maturation of a T-cell response. We are beginning to understand the power of co-inhibitors in the context of lymphocyte homeostasis and the pathogenesis of leukemia, which involves several newly described co-inhibitory pathways, including the programmed death-1 (PD-1) and PD-1 ligand (PD-L1) pathway. The aim of this review is to summarize the PD-1 and PD-L1 biological functions and their alterative expression in hematological malignancies. The role of PD-1 and PD-L1 in T-cell immune suppression and the potential for immunotherapy via blocking PD-1 and PD-L1 in hematological malignancies are also reviewed.

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Author and article information

Contributors

Ling Xu: lingxu114@163.com

Yikai Zhang: jnuyikai@163.com

Gengxin Luo: jdluogx@163.com

Yangqiu Li: yangqiuli@hotmail.com

Journal

Journal ID (nlm-ta): J Hematol Oncol

Journal ID (iso-abbrev): J Hematol Oncol

Title: Journal of Hematology & Oncology

Publisher: BioMed Central (London )

ISSN (Electronic): 1756-8722

Publication date (Electronic): 14 October 2015

Publication date PMC-release: 14 October 2015

Publication date Collection: 2015

Volume: 8

Electronic Location Identifier: 113

Affiliations

[ ]Department of Hematology, First Affiliated Hospital, Jinan University, Guangzhou, 510632 China

[ ]Institute of Hematology, Jinan University, Guangzhou, 510632 China

[ ]Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, 510632 China

Article

Publisher ID: 214

DOI: 10.1186/s13045-015-0214-5

PMC ID: 4605076

PubMed ID: 26462561

SO-VID: a8c536cd-1f63-4e81-a83c-4a907de227cf

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 6 August 2015

Date accepted : 1 October 2015

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: stem cell memory t cells,adoptive cell therapy,hematological malignancy,antigen-specific t cells

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: stem cell memory t cells, adoptive cell therapy, hematological malignancy, antigen-specific t cells

The roles of stem cell memory T cells in hematological malignancies

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Stress signalling in stem cells

Most cited references 36

IL-7 and IL-15 instruct the generation of human memory stem T cells from naive precursors.

Superior T memory stem cell persistence supports long-lived T cell memory.

The role of PD-1 and PD-L1 in T-cell immune suppression in patients with hematological malignancies

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