Worsening Graft-Versus-Host Disease with Anti-PD1 Treatment in a Mouse Model of Fungal Infection

Fungal infection can occur after hematopoietic stem cell transplantation (allow-HSCT). Graft-versus-host disease (GVHD) often occurs simultaneously with fungal infection and promotes each other. However, the mechanism underlying those reciprocal influences is poorly understood. This study showed that zymosan, an important component of yeast cell wall, can augment GVHD in an MHC-matched mouse GVHD model (H2d to H2d) based on busulfan and fludarabine. Zymosan reduced donor alternatively activated macrophages (M2). Unlike some reversed effect reports in zymosan model using anti-PD1 (and/or anti-Gr1) treatment, this study showed that GVHD worsened with anti-PD1 treatment in the zymosan GVHD mouse model. The worsening graft-versus-host disease with anti-PD1 treatment was associated with the reduction of Tregs. The results suggest that therapies that block PD-L1/PD-1 in parenchymal tissues in the recipient could worsen GVHD in humans, especially in the presence of infection or inflammation.