MTOR activity and metabolic reprogramming of CD8+ T cells is impaired under hypoxia and within the multiple myeloma bone marrow.

ABSTRACT:

Abstract

Novel therapies for multiple myeloma (MM) aim to engage antitumor functions of T cells. However, evidence indicates these functions are limited within the bone marrow (BM) environment. This is relatively hypoxic in health, and studies indicate widespread hypoxia in MM. In this study, CD8+ T-cell responses to stimulation were assessed under hypoxia, which identified that activation, proliferation, and interferon-gamma (IFN-γ) secretion were profoundly suppressed, while cytotoxicity and tumor necrosis factor-α (TNF-α) expression were unaffected. These changes occurred alongside decreased mechanistic target of rapamycin (mTOR) activity and expression of c-Myc, which drives T-cell metabolic reprogramming upon stimulation. Consistently, hypoxic CD8+ T cells demonstrated decreas

SUBMITTER: Fulton-Ward T 

PROVIDER: S-EPMC12719155 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature