Figure 4.
Sequential CD19 and CD20 loss and branching evolution in lymphoma under the pressure of T-cell–redirecting immunotherapy. (A) Schematic timeline of the treatment history and sampling from patient 1 around the 4 sampling time points. Samples 1.2 and 1.4 were both obtained from a lymph node lesion at the left clavicula during CD20 bispecs and 80 days later, respectively. (B) CD79A, CD19, and CD20 protein expression determined using IHC on FFPE biopsy sections of sample 1.2 showing CD19/CD20 double-negative tumor after CD19 CAR T and CD20 bispec treatment, demonstrating sequential antigen loss. (C) Log-normalized MS4A1 expression color-coded and projected on the UMAP representation of sample 1.4 B cells/malignant cells demonstrates the recurrence of MS4A1-positive cells at a single-cell transcriptomic level. (D) Bar plot showing the proportion of MS4A1 expressing cells, determined by at least 1 count of MS4A1. (E) CD79A and CD20 protein expression determined using IHC on FFPE biopsy sections of sample 1.4 with a partially positive CD20 stain, validating CD20 recurrence on protein level. (F) Schematic timeline of the treatment history and sampling of patient 2 around the 4 sampling time points of samples that were subjected to WES (2.2, 2.4 or 2.5, 2.7, and 2.8). Sample ID, site, CD19 status, and CD20 status are indicated. (G) Mock phylogenetic tree constructed from SciClone clusters (indicated by colors) based on WES. The number at the start edge indicates the number of aberrations in the most recent common ancestor, and numbers on branches indicate the amount of acquired mutations. Length of branches does not indicate the extent of differences between subclones. Samples corresponding to subclone branches are indicated; see supplemental Figure 10 for details. IN, inguinal.

Sequential CD19 and CD20 loss and branching evolution in lymphoma under the pressure of T-cell–redirecting immunotherapy. (A) Schematic timeline of the treatment history and sampling from patient 1 around the 4 sampling time points. Samples 1.2 and 1.4 were both obtained from a lymph node lesion at the left clavicula during CD20 bispecs and 80 days later, respectively. (B) CD79A, CD19, and CD20 protein expression determined using IHC on FFPE biopsy sections of sample 1.2 showing CD19/CD20 double-negative tumor after CD19 CAR T and CD20 bispec treatment, demonstrating sequential antigen loss. (C) Log-normalized MS4A1 expression color-coded and projected on the UMAP representation of sample 1.4 B cells/malignant cells demonstrates the recurrence of MS4A1-positive cells at a single-cell transcriptomic level. (D) Bar plot showing the proportion of MS4A1 expressing cells, determined by at least 1 count of MS4A1. (E) CD79A and CD20 protein expression determined using IHC on FFPE biopsy sections of sample 1.4 with a partially positive CD20 stain, validating CD20 recurrence on protein level. (F) Schematic timeline of the treatment history and sampling of patient 2 around the 4 sampling time points of samples that were subjected to WES (2.2, 2.4 or 2.5, 2.7, and 2.8). Sample ID, site, CD19 status, and CD20 status are indicated. (G) Mock phylogenetic tree constructed from SciClone clusters (indicated by colors) based on WES. The number at the start edge indicates the number of aberrations in the most recent common ancestor, and numbers on branches indicate the amount of acquired mutations. Length of branches does not indicate the extent of differences between subclones. Samples corresponding to subclone branches are indicated; see supplemental Figure 10 for details. IN, inguinal.

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