Single-Cell RNA-seq Analysis Reveals Distinct Tumor and Immunosuppressive T-Cell Phenotypes in Patients with CLL Treated with Ibrutinib

Shanmugapriya Thangavadivel; Jami Shaffer; Shrilekha Misra; Samon Benrashid; Britten Gordon; Alexander He; Wantong Li; Konur Oyman; Annika Chura; Shelby Cabrera; Altan Turkoglu; Tzung-Huei Lai; Kerry A. Rogers; Seema A. Bhat; John C. Byrd; James S. Blachly; Jennifer A. Woyach; Bradley W. Blaser

doi:10.1158/1078-0432.ccr-25-3349

Key Points

This research aims to explore the variations in tumor and immune cell characteristics in CLL patients receiving ibrutinib treatment.
Utilized single-cell RNA-sequencing analysis to assess transcriptional profiles.
Examined the tumor and immune cell environments in patients.
Identified T-cell and monocyte phenotypes associated with treatment resistance.
Observed distinct transcriptional changes in circulating immune cells linked to ibrutinib resistance.
Identified increased signs of T-cell exhaustion in the immune milieu of treated patients.
Monocyte polarization was associated with long-term treatment effects, indicating its role in resistance.

Implication

Analysis reveals transcriptional changes linked to resistance in CLL patients treated with ibrutinib, suggesting immune response impact.

Abstract

At single-cell level, our findings demonstrate a picture of transcriptional heterogeneity in the tumor compartment and immune milieu. Overall, these findings highlight transcriptional changes in circulating immune cells associated with ibrutinib resistance, suggesting that T-cell exhaustion and monocyte polarization accompany and may contribute to resistance during long-term BTKi therapy.

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Cite This Study

Thangavadivel et al. (2026) studied this question.

synapsesocial.com/papers/69eb092b553a5433e34b3ba7 https://doi.org/10.1158/1078-0432.ccr-25-3349

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Single-Cell RNA-seq Analysis Reveals Distinct Tumor and Immunosuppressive T-Cell Phenotypes in Patients with CLL Treated with Ibrutinib

Key Points

Implication

Abstract

Discussion

Cite This Study

Single-Cell RNA-seq Analysis Reveals Distinct Tumor and Immunosuppressive T-Cell Phenotypes in Patients with CLL Treated with Ibrutinib

Key Points

Implication

Abstract

Discussion

Cite This Study

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