Rewiring mitochondrial metabolism to counteract exhaustion of CAR-T cells

Yue Huang; Xiaohui Si; Mi Shao; Xinyi Teng; Gang Xiao; He Huang

doi:10.1186/s13045-022-01255-x

Rewiring mitochondrial metabolism to counteract exhaustion of CAR-T cells

J Hematol Oncol. 2022 Mar 28;15(1):38. doi: 10.1186/s13045-022-01255-x.

Authors

Yue Huang^#^{1

2

3

4}, Xiaohui Si^#^{1

2

3

4}, Mi Shao^{1

2

3

4}, Xinyi Teng^{1

2

3

4}, Gang Xiao^{5

6

7

8}, He Huang^{9

10

11

12}

Affiliations

¹ Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, China.
² Liangzhu Laboratory, Zhejiang University Medical Center, 1369 West Wenyi Road, Hangzhou, China.
³ Institute of Hematology, Zhejiang University, Hangzhou, China.
⁴ Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China.
⁵ Liangzhu Laboratory, Zhejiang University Medical Center, 1369 West Wenyi Road, Hangzhou, China. gxiao@zju.edu.cn.
⁶ Institute of Hematology, Zhejiang University, Hangzhou, China. gxiao@zju.edu.cn.
⁷ Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China. gxiao@zju.edu.cn.
⁸ Institute of Immunology, Zhejiang University, Hangzhou, China. gxiao@zju.edu.cn.
⁹ Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, China. huanghe@zju.edu.cn.
¹⁰ Liangzhu Laboratory, Zhejiang University Medical Center, 1369 West Wenyi Road, Hangzhou, China. huanghe@zju.edu.cn.
¹¹ Institute of Hematology, Zhejiang University, Hangzhou, China. huanghe@zju.edu.cn.
¹² Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China. huanghe@zju.edu.cn.

^# Contributed equally.

Abstract

Short persistence and early exhaustion of T cells are major limits to the efficacy and broad application of immunotherapy. Exhausted T and chimeric antigen receptor (CAR)-T cells upregulate expression of genes associated with terminated T cell differentiation, aerobic glycolysis and apoptosis. Among cell exhaustion characteristics, impaired mitochondrial function and dynamics are considered hallmarks. Here, we review the mitochondrial characteristics of exhausted T cells and particularly discuss different aspects of mitochondrial metabolism and plasticity. Furthermore, we propose a novel strategy of rewiring mitochondrial metabolism to emancipate T cells from exhaustion and of targeting mitochondrial plasticity to boost CAR-T cell therapy efficacy.

Keywords: CAR-T cell exhaustion; Metabolism; Mitochondria; Single-cell techniques.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Humans
Immunotherapy
Immunotherapy, Adoptive*
Lymphocyte Activation
Mitochondria / metabolism
T-Lymphocytes*

Abstract

Publication types

MeSH terms

Grants and funding