PD1+TIGIT+2B4+KLRG1+ Cells Might Underlie T Cell Dysfunction in Patients Treated with BCMA-Directed Chimeric Antigen Receptor T Cell Therapy. Transplant Cell Ther 2024 Feb;30(2):191-202
Date
11/16/2023Pubmed ID
37967650DOI
10.1016/j.jtct.2023.11.014Scopus ID
2-s2.0-85180592139 (requires institutional sign-in at Scopus site) 5 CitationsAbstract
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.
Author List
Mishra AK, Schmidt TM, Martell EB, Chen AS, Dogru RE, Hematti P, Callander NSAuthor
Peiman Hematti MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
B-Cell Maturation AntigenCell- and Tissue-Based Therapy
Humans
Lectins, C-Type
Multiple Myeloma
Neoplasm Recurrence, Local
Receptors, Immunologic
Recurrence
