PD1(+)TIGIT(+)2B4(+)KLRG1(+) 细胞可能是 BCMA 靶向 CAR-T 细胞治疗患者 T 细胞功能障碍的根源

Chimeric antigen receptor T cell (CAR-T) therapy has shown rapid, frequent, and deep responses in patients with relapsed/refractory multiple myeloma (RRMM).

However, relapse frequently occurs following CAR-T therapy, and the cause of this resistance is not well defined. Among the potential mechanisms of resistance, T cell intrinsic factors may be an important source of failure.

Here we used spectral flow cytometry to identify the changes in T cell phenotypes in bone marrow aspirates at different stages of multiple myeloma progression, including cases that relapsed after anti-BCMA CAR-T therapy.

We identified completely different T cell phenotypes in RRMM and post CAR-T relapse cases compared to healthy donors and earlier stages of multiple myeloma, novel double-negative CD3 + T cells in RRMM and CAR-T relapsed cases, and differences in CD8 T cell phenotype at the baseline between peripheral blood and bone marrow from healthy donors.

We found that the majority of T cells in RRMM patients and significant T cell subsets in post-CAR-T relapsed patients expressed multiple coinhibitory markers, including PD1, TIGIT, 2B4, and KLRG1.