Primary prophylaxis with mTOR inhibitor enhances T-cell effector function and prevents heart transplant rejection during talimogene laherparepvec therapy of squamous cell carcinoma

Longitudinal analysis of PBMC immune phenotype and T cell activation/negative regulation profile in a solid organ transplanted patient with cutaneous squamous cell carcinoma treated with talimogene laherparepvec therapy
Conclusion:
Longitudinal analysis of systemic immunologic changes was observed in a male patient with metastatic cutaneous squamous cell carcinoma and heart transplantation. Calcineurin inhibitor/ mycophenolic acid replaced by mTOR inhibitor everolimus improved effector T-cell status with increased cytotoxic activity, proliferation and activation. Talimogene laherparepvec injection enhanced effector function by switching CD4/CD8 T-cells from central memory to effector memory profiles, enhanced Th1 responses, and increased cytotoxic and proliferative activities. These findings provide valuable insights into the dynamics of T-cell activation and differentiation which suggest that timely initiation of mTORi-based primary prophylaxis may provide a dual benefit of revitalizing T-cell function while maintaining allograft tolerance. Antibodies were titrated for optimal stain profile and 74 reference samples of healthy donors were used to establish baseline marker expression. Samples were loaded with EQ beads (Standard BioTools) and data were normalized using a bead-based normalization algorithm (Standard BioTools).