Hypoxia promotes BCMA loss and a suppressive secretome thereby hindering CAR T cell therapy in multiple myeloma.

ABSTRACT:

Introduction

Multiple myeloma (MM) develops in the hypoxic bone marrow (BM) microenvironment, which alters tumor behavior and immune responses. While hypoxia is known to directly suppress immune function, its effect on immunotherapy-relevant antigen expression and the MM secretome remains underexplored. Here, we investigated how hypoxia affects BCMA expression and BCMA-targeted CAR T cell responses.

Methods

MM cells were cultured under normoxia (21% O₂) or hypoxia (1% O₂). BCMA surface and total expression were analyzed. Anti-BCMA CAR T cells were co-cultured with normoxic or hypoxic MM cells to assess cytotoxicity and cytokine release. Conditioned media and small extracellular vesicles (sEVs) were isolated, quantified, and RNA-profiled.

Results

MM cells cultured in h

SUBMITTER: Tu C 

PROVIDER: S-EPMC12781295 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature