Assessment of Tfh Cells and Related Molecules in CML-CP Patients With Different Molecular Responses.

Abstract

Introduction: This study aimed to characterize T follicular helper (Tfh) cell differentiation and related molecular profiles in chronic-phase chronic myeloid leukemia (CML-CP) patients with distinct molecular responses and to explore immune correlates of treatment outcomes.

Methods: Peripheral blood CD4⁺ T cells were analyzed in 125 CML-CP patients (8 newly diagnosed, 71 MMR, and 46 pre-MMR) and 22 healthy donors. We assessed CD4⁺ T subset distribution and expression of Tfh-related molecules including Bcl6, Blimp1, PD-1, PD-L1, and PD-L2.

Results: Newly diagnosed and pre-MMR patients exhibited decreased CD4⁺ T cell proportions compared to healthy donors and MMR patients (p < 0.05), while pre-MMR patients had elevated frequencies of CD4⁺CXCR5⁺PD-1⁺ Tfh cells and increased PD-1 expression on CD4⁺ T cells (p < 0.05). Bcl6, PD-1, and PD-L1 were upregulated in pre-MMR cases, whereas Blimp1 and PD-L2 remained unaltered.

Conclusion: Pre-MMR CML-CP is accompanied by aberrant Tfh cell differentiation and an immunosuppressive immune signature linked to suboptimal molecular responses. Targeting immune checkpoints or modulating Tfh cell homeostasis may help improve therapeutic outcomes in CML-CP.