New Insights Into Factors Shaping CMV-Specific T-Cell Polyfunctionality After Hematopoietic Cell Transplantation.

Area of Science:

• Immunology
• Transplantation Medicine
• Virology

Background:

• Polyfunctional T cells are vital for controlling cytomegalovirus (CMV) after allogeneic hematopoietic cell transplantation (HCT).
• Managing refractory CMV and optimizing virus-specific cellular therapy (VST) remain challenges in HCT recipients.

Purpose of the Study:

• To comparatively analyze how the timing and dosing of immunosuppressive agents impact CMV-specific T-cell polyfunctionality in HCT patients.
• To identify specific immunosuppressive drug regimens that may impair or preserve T-cell responses against CMV.

Main Methods:

• Assessed CD4+ and CD8+ T-cell responses (IFN-γ plus ≥1 functional marker) following pp65 stimulation in 243 HCT recipients within 100 days post-HCT.
• Compared the effects of post-transplant cyclophosphamide (PT-Cy), corticosteroids, mycophenolate mofetil (MMF), and calcineurin inhibitors (CNIs) on T-cell polyfunctionality.
• Analyzed responses in both pre- and post-letermovir eras.

Main Results:

• Post-transplant cyclophosphamide (PT-Cy) did not significantly impair T-cell functionality.
• Cyclosporine was associated with higher polyfunctional T-cell frequencies than tacrolimus, irrespective of concentration.
• Intermediate to high-dose corticosteroids, particularly when given within 2-4 weeks before testing, suppressed T-cell responses, though rapid tapering mitigated this effect.
• Prolonged administration of mycophenolate mofetil (MMF) diminished T-cell polyfunctionality.

Conclusions:

• The timing and dosage of immunosuppressive agents like corticosteroids and MMF significantly influence CMV-specific T-cell polyfunctionality post-HCT.
• Cyclosporine may be preferable to tacrolimus for preserving T-cell responses.
• Adjusting immunosuppression strategies, considering specific drug timing and dosing, could improve CMV management and VST efficacy in HCT recipients.