PD1+TIGIT+2B4+KLRG1+Cells Might Underlie T Cell Dysfunction in Patients Treated with BCMA-Directed Chimeric Antigen Receptor T Cell Therapy

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. (c) 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.