Memory T cells: strategies for optimizing tumor immunotherapy

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Abstract

Several studies have demonstrated that memory T cells including stem cell memory (Tscm) T cells and central memory (Tcm) T cells show superior persistence and antitumor immunity compared with effector memory T (Tem) cells and effector T (Teff) cells. Furthermore, the Tcm/Teff ratio has been reported to be a predictive biomarker of immune responses against some tumors. Thus, a system-level understanding of the mechanisms underlying the differentiation of effector and memory T cells is of increasing importance for developing immunological strategies against various tumors. This review focuses on recent advances in efficacy against tumors, the origin, formation mechanisms of memory T cells, and the role of the gut microbiota in memory T cell formation. Furthermore, we summarize strategies to generate memory T cells in ( ex) vivo that, might be applicable in clinical practice.

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A defined commensal consortium elicits CD8 T cells and anti-cancer immunity

Takeshi Tanoue, Satoru Morita, Damian R Plichta … (2019)

There is a growing appreciation for the importance of the gut microbiota as a therapeutic target in various diseases. However, there are only a handful of known commensal strains that can potentially be used to manipulate host physiological functions. Here we isolate a consortium of 11 bacterial strains from healthy human donor faeces that is capable of robustly inducing interferon-γ-producing CD8 T cells in the intestine. These 11 strains act together to mediate the induction without causing inflammation in a manner that is dependent on CD103+ dendritic cells and major histocompatibility (MHC) class Ia molecules. Colonization of mice with the 11-strain mixture enhances both host resistance against Listeria monocytogenes infection and the therapeutic efficacy of immune checkpoint inhibitors in syngeneic tumour models. The 11 strains primarily represent rare, low-abundance components of the human microbiome, and thus have great potential as broadly effective biotherapeutics.

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Recapitulating adult human immune traits in laboratory mice by normalizing environment

Lalit Beura, Sara Hamilton, Kevin Bi … (2016)

Our current understanding of immunology was largely defined in laboratory mice because of experimental advantages including inbred homogeneity, tools for genetic manipulation, the ability to perform kinetic tissue analyses starting with the onset of disease, and tractable models. Comparably reductionist experiments are neither technically nor ethically possible in humans. Despite revealing many fundamental principals of immunology, there is growing concern that mice fail to capture relevant aspects of the human immune system, which may account for failures to translate disease treatments from bench to bedside 1–8 . Laboratory mice live in abnormally hygienic “specific pathogen free” (SPF) barrier facilities. Here we show that the standard practice of laboratory mouse husbandry has profound effects on the immune system and that environmental changes result in better recapitulation of features of adult humans. Laboratory mice lack effector-differentiated and mucosally distributed memory T cells, which more closely resembles neonatal than adult humans. These cell populations were present in free-living barn populations of feral mice, pet store mice with diverse microbial experience, and were induced in laboratory mice after co-housing with pet store mice, suggesting a role for environment. Consequences of altering mouse housing profoundly impacted the cellular composition of the innate and adaptive immune system and resulted in global changes in blood cell gene expression patterns that more closely aligned with immune signatures of adult humans rather than neonates, altered the mouse’s resistance to infection, and impacted T cell differentiation to a de novo viral infection. These data highlight the impact of environment on the basal immune state and response to infection and suggest that restoring physiological microbial exposure in laboratory mice could provide a relevant tool for modeling immunological events in free-living organisms, including humans.

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Lineage relationship and protective immunity of memory CD8 T cell subsets.

E. John Wherry, Volker Teichgräber, Todd C. Becker … (2003)

Memory CD8 T cells can be divided into two subsets, central (T(CM)) and effector (T(EM)), but their lineage relationships and their ability to persist and confer protective immunity are not well understood. Our results show that T(CM) have a greater capacity than T(EM) to persist in vivo and are more efficient in mediating protective immunity because of their increased proliferative potential. We also demonstrate that, following antigen clearance, T(EM) convert to T(CM) and that the duration of this differentiation is programmed within the first week after immunization. We propose that T(CM) and T(EM) do not necessarily represent distinct subsets, but are part of a continuum in a linear naive --> effector --> T(EM) --> T(CM) differentiation pathway.

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Author and article information

Contributors

Zhongjie Sun: szj@newishes.com

Ligong Chen:

ORCID: http://orcid.org/0000-0002-7893-7173

ligongchen@tsinghua.edu.cn

Journal

Journal ID (nlm-ta): Protein Cell

Journal ID (iso-abbrev): Protein Cell

Title: Protein & Cell

Publisher: Higher Education Press (Beijing )

ISSN (Print): 1674-800X

ISSN (Electronic): 1674-8018

Publication date (Electronic): 27 March 2020

Publication date PMC-release: 27 March 2020

Publication date (Print): August 2020

Volume: 11

Issue: 8

Pages: 549-564

Affiliations

[1 ]GRID grid.12527.33, ISNI 0000 0001 0662 3178, School of Pharmaceutical Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), , Tsinghua University, ; Beijing, 100084 China

[2 ]Newish Technology (Beijing) Co., Ltd., Xihuan South Road 18, Economic & Technical Development Zone, Beijing, 100176 China

[3 ]Moon (Guangzhou) Biotech Co., Ltd., Room 301, Building B5, Enterprise Accelerator, No. 11 Kaiyuan Avenue, Huangpu District, Guangzhou, 510000 China

[4 ]GRID grid.24696.3f, ISNI 0000 0004 0369 153X, Advanced Innovation Center for Human Brain Protection, Beijing Tiantan Hospital, , Capital Medical University, ; Beijing, 100088 China

Author information

Qingjun Liu http://orcid.org/0000-0002-8923-3921

Ligong Chen http://orcid.org/0000-0002-7893-7173

Article

Publisher ID: 707

DOI: 10.1007/s13238-020-00707-9

PMC ID: 7381543

PubMed ID: 32221812

SO-VID: 1d492e4b-6af2-4d70-b937-97765316a2b3

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 31 December 2019

Date accepted : 8 March 2020

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Keywords: memory t cells,tumor immunology,metabolism,gut microbiota

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Keywords: memory t cells, tumor immunology, metabolism, gut microbiota

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Memory T cells: strategies for optimizing tumor immunotherapy

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Embodied Memory

Most cited references 92

A defined commensal consortium elicits CD8 T cells and anti-cancer immunity

Recapitulating adult human immune traits in laboratory mice by normalizing environment

Lineage relationship and protective immunity of memory CD8 T cell subsets.

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