肿瘤内在 CD21 表达影响 B 细胞恶性肿瘤细胞对 CD19-CAR-T 细胞的应答

CD19-chimeric antigen receptor (CAR)-based T-cell therapy has produced promising clinical responses in patients with relapsed or refractory B-cell malignancies.

However, a significant portion of patients with mature B cell-derived malignancies, including chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma (NHL), do not respond to CD19-CAR-T cell therapy. Whether any characteristics and biomarkers intrinsic to cancer cells themselves can predict the CD19-CAR-T cell therapeutic response remains largely unknown.

Surprisingly, by using experimental models, we show here that malignant B cells bearing CD21, a mature B cell marker, could not be efficiently killed by CD19-CAR-T cells. CD19, CD21, and CD81, together with CD225, form the B cell coreceptor complex that enhances B cell-mediated signaling.

Our results indicated that CD21 affected the recognition of CD19-positive tumor cells by CD19-CAR-T cells and impaired the antitumor capacities of these effector cells.

We have not only uncovered a mechanism underlying the impairment of CD19-CAR-T cells in mature B cell-derived CLL and NHL, but also proposed a pretreatment biomarker that may predict CD19-CAR-T cell therapeutic response, thus preventing foreseeable therapy failure and suggesting optimal personized therapies.