American Association for Cancer Research

sorry, we can't preview this file

23266066cir200252-sup-240559_3_supp_6514607_qfg9ft.docx (1.36 MB)

Supplementary Figure 4 from Long-term Sculpting of the B-cell Repertoire following Cancer Immunotherapy in Patients Treated with Sipuleucel-T

Download (1.36 MB)
journal contribution
posted on 2023-04-04, 01:03 authored by Li Zhang, Harini Kandadi, Hai Yang, Jason Cham, Tao He, David Y. Oh, Nadeem A. Sheikh, Lawrence Fong

Supplementary Fig. 4: (A-D) BCR convergent groups converge to shared amino acid sequences. (A-B) Phylogenetic trees across all repertories of a representative naive patient (A) and of a representative treated patient (B). For each patient, social network analysis was performed using R packages: Ape (24) and igraph (25). A convergent group was defined as a cluster that includes the clones with the distance less than or equal to 1 (allowing maximum of 1 basepair mutation among clone sequences sharing the same V-gene, J-gene and CDR3 length). The phylogenetic tree was plotted by R package: ggtree (26) with the edge color was coded by amino acid sequences. (C) Social network of a selected V family (V01) across all repertories from the 6 time points of the representative treated patient. Each node represents a single full-length of BCR clonotype sequence colored by its corresponding CDR3 amino acid sequences; node size was characterized based on the corresponding abundance. The nodes connected by lines were within the same convergent group. (D) Social network figures of top 6 largest groups in the V01 family across all repertories from the 6 time points of the representative treated patient in (C). One convergent group was selected for illustration purpose with presenting the actual converged two CDR3 amino acid sequences. (E) Public clusters shared by treated patients at baseline and naïve patients post baseline. Across all repertories from treated patients at baseline and naïve patients post baseline, 5 public clones were identified first. Then social network analysis was performed to find the clones which were at most 1 basepair mismatch with those 5 public clones.



Conquer Cancer Foundation of the American Society of Clinical Oncology

Prostate Cancer Foundation Young Investigator Award

Prostate Cancer Foundation



Sipuleucel-T is an autologous cellular immunotherapy, administered as three infusions, for metastatic castration-resistant prostate cancer (mCRPC). Sipuleucel-T induces T- and B-cell responses to prostatic acid phosphatase (PAP), correlating to improved survival. The long-term impact of sipuleucel-T on tumor antigen–specific immunologic memory remains unknown, in particular, B-cell responses, as measured by antigen-specific antibody responses and B-cell receptor (BCR) sequences. To evaluate whether sipuleucel-T could induce long-term immunologic memory, we examined circulating B-cell responses before and after sipuleucel-T treatment in two groups of patients with mCRPC: those who had previously received sipuleucel-T (treated; median, 8.9 years since the previous treatment) versus those who had not (naïve). Before re-treatment, previously treated patients exhibited persistent antibody responses as well as more focused and convergent BCR repertoires with distinct V(D)J gene usage compared with naïve patients. After re-treatment, previously treated patients maintained high-frequency clones and developed more convergent BCRs at earlier time points unlike naïve patients. With the first sipuleucel-T infusion specifically, previously treated patients had less shuffling within the 100 most abundant baseline clones. In contrast, naïve patients exhibited great BCR turnover with a continued influx of new B-cell clones. Social network analysis showed that previously treated patients had more highly organized B-cell repertoires, consistent with greater clonal maturation. Higher treatment-induced BCR clonality correlated with longer survival for naïve patients. These results demonstrated the capacity of sipuleucel-T to induce long-term immune memory and lasting changes to the B-cell repertoire.

Usage metrics

    Cancer Immunology Research



    Ref. manager