14B. Immune Profiling in Pediatric Cancer (2)

There is an urgent need to enhance survival chances post-hematopoietic cell transplantation (HCT), as still 30-50% of pediatric HCT-recipients die from immune-related complications, such as graft-versus-host disease, viral reactivations, and/or relapse. Our recent work on the importance of CD4+ T-cell reconstitution for a better outcome, prompted the acceptance of CD4+ T-cell counts as objective endpoint parameter in clinical studies (eg. by the FDA). Nevertheless, CD4+ T-cell numbers alone do not allow for prediction and/or treatment stratification of individual patients. We hypothesize that the interplay between regulatory and stimulatory T-cell functions is a decisive factor influencing the occurrence and management of HCT complications. With the use of parameters indicating T-cell function, rather than only numbers, we expect to be able to better predict HCT complications, leading to a more efficient, personalized treatment approach with less toxicity and better survival chances.

The aim of this proposal is to decipher the function of T-cell subsets post-HCT to 1) study the underlying mechanism of immune-regulation and -dysregulation, and 2) identify immune-based predictors to personalize prevention- and treatment of inflammatory complications.