Omics · study · 2026
Patient-Derived Lymphoma Spheroids Reveal Predictive Markers of Glofitamab Resistance in Relapsed/Refractory B-NHL
Listed in NCBI GEO
Bispecific antibodies (bsAbs) such as glofitamab represent a promising therapeutic approach for relapsed/refractory B-cell non-Hodgkin's lymphoma (R/R B-NHL), but resistance mechanisms remain poorly understood.
Description
This study aimed to identify predictive markers of bsAbs resistance based on the response of 3D patient-derived lymphoma spheroids (PDLS) established from R/R B-NHL samples. PDLS were treated with 0.1 nM glofitamab for 3 days and B-cell depletion was quantified as measure of ex vivo treatment response.
Comprehensive immune profiling were performed on patient samples using multiparametric flow cytometry, single-cell RNA sequencing, CODEX spatial proteomics and functional assays. This study revealed that high responders to glofitamab possessed more activated CD8+ T-cells with higher cytotoxic signatures, while low responders showed enriched exhausted CD8+ T-cell populations with enhanced expression of exhaustion markers (TIGIT, LAG3, PD1).
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Moreover, low responders demonstrated elevated functional CD4+ T-follicular helper (Tfh) cells in close proximity to malignant B-cell thus promoting their survival through IL21 and CXCL13 signaling pathways. Functional experiments have shown that adding anti-TIGIT co-treatment enhanced glofitamab efficacy in low responder samples, and Tfh depletion improved cytotoxic T-cell function. Our findings identify CD8+ T-cell exhaustion and functionally activated Tfh cells as key resistance mechanisms to glofitamab in R/R B-NHL.
Targeting these pathways represents a promising strategy to overcome bsAb resistance and improving therapeutic outcomes.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE306nnn/GSE306092 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE306092 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1309107 ncbi.nlm.nih.gov/bioproject/PRJNA1309107 ↗
project · from NCBI GEO
- PubMed 41746860 pubmed.ncbi.nlm.nih.gov/41746860 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Mass spectrometry 65% · RNA sequencing 75% · Sequencing 75% · Single-cell RNA sequencing 75%
Provenance · 1 source records, 11 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE306092 | 14 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:mass-spectrometry | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:sequencing | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:single-cell-rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |