Senescent T cells within suppressive tumor microenvironments: emerging target for tumor immunotherapy

X Liu, DF Hoft, G Peng - The Journal of clinical investigation, 2020 - Am Soc Clin Investig
X Liu, DF Hoft, G Peng
The Journal of clinical investigation, 2020Am Soc Clin Investig
The functional state of the preexisting T cells in the tumor microenvironment is a key
determinant for effective antitumor immunity and immunotherapy. Increasing evidence
suggests that immunosenescence is an important state of T cell dysfunction that is distinct
from exhaustion, a key strategy used by malignant tumors to evade immune surveillance
and sustain the suppressive tumor microenvironment. Here, we discuss the phenotypic and
functional characteristics of senescent T cells and their role in human cancers. We also …
The functional state of the preexisting T cells in the tumor microenvironment is a key determinant for effective antitumor immunity and immunotherapy. Increasing evidence suggests that immunosenescence is an important state of T cell dysfunction that is distinct from exhaustion, a key strategy used by malignant tumors to evade immune surveillance and sustain the suppressive tumor microenvironment. Here, we discuss the phenotypic and functional characteristics of senescent T cells and their role in human cancers. We also explore the possible mechanisms and signaling pathways responsible for induction of T cell senescence by malignant tumors, and then discuss potential strategies to prevent and/or reverse senescence in tumor-specific T cells. A better understanding of these critical issues should provide novel strategies to enhance cancer immunotherapy.
The Journal of Clinical Investigation