Deletion of Cbl-b inhibits CD8⁺ T-cell exhaustion and promotes CAR T-cell function.

ABSTRACT:

Background

Chimeric antigen receptor (CAR) T-cell therapy is an emerging option for cancer treatment, but its efficacy is limited, especially in solid tumors. This is partly because the CAR T cells become dysfunctional and exhausted in the tumor microenvironment. However, the key pathways responsible for impaired function of exhausted cells remain unclear, which is essential to overcome CAR T-cell exhaustion.

Methods

Analysis of RNA-sequencing data from CD8⁺ tumor-infiltrating lymphocytes (TILs) led to identification of Cbl-b as a potential target. The sequencing data were validated using a syngeneic MC38 colon cancer model. To analyze the in vivo role of Cbl-b in T-cell exhaustion, tumor growth, % PD1⁺Tim3⁺ cells, and expression of effector

SUBMITTER: Kumar J 

PROVIDER: S-EPMC7813298 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature