Bone marrow-derived mesenchymal stromal cells obstruct AML-targeting CD8⁺ clonal effector and CAR T-cell function...

Area of Science:

• Immunology
• Oncology
• Cell Biology

Background:

• Mesenchymal stromal cells (MSCs) are known immunomodulators.
• Their impact on T-cell-based immunotherapy for acute myeloid leukemia (AML) requires further investigation.

Purpose of the Study:

• To determine if MSCs impede anti-leukemic T-cell activity.
• To investigate MSC-induced T-cell senescence in AML immunotherapy.

Main Methods:

• Co-culture of MSCs with leukemia-specific cytotoxic T-lymphocytes (CTLs) and chimeric antigen receptor (CAR) T cells.
• Assessment of T-cell cytotoxicity, cytokine secretion, expansion, and senescence markers (CD28-, CD57+).

Main Results:

• MSCs inhibited CAR T-cell expansion via indoleamine 2,3-dioxygenase 1 (IDO-1) activity.
• MSCs reduced interferon gamma (IFNγ) and interleukin-2 (IL-2) release from CTLs and CAR T cells.
• MSCs induced a senescent T-cell phenotype (CD28loCD27loCD57+KLRG1+).

Conclusions:

• MSCs are potent inhibitors of anti-leukemic T cells.
• Targeting MSCs' mechanisms could enhance AML immunotherapy efficacy.