This project focuses on dissecting tumor-reactive T and NK cell responses after donor stem cell transplantation and exploration of adjuvant immunotherapeutic strategies to further boost anti-tumor immunity in these patients. Interested in Cancer Immunology and Immunotherapy and pursuing a PhD career? Join our exciting translational research group! Every year, approximately 850 new patients are diagnosed with acute myeloid leukemia (AML). More than 50% of these patients have poor risk based on unfavorable mutations or cytogenetics or poor response to initial therapy. Allogeneic stem cell transplantation (alloSCT) is the only curative treatment option for poor-risk AML. Nevertheless, relapse rates are up to 40%.
Donor-derived NK and T cells play a crucial role in the curative graft-versus-tumor (GVT) response in AML patients after alloSCT. Robust alloreactive NK and T cell responses can be elicited, resulting in the establishment of clinical remission. Notably, a small pool of long-lived alloreactive memory T cells remains, which plays an important role in protective immune surveillance. Unfortunately, the beneficial GVT effect may be accompanied by graft-versus-host disease (GVHD). GVHD is the major cause of morbidity and non-relapse mortality after alloSCT. Therefore, various approaches to deplete alloreactive T cells, and thereby prevent GVHD, are applied in the clinic. The counter side of such strategies is increased risk of relapse. Hence, it is essential to minimize GVHD while preserving GVT immunity.
This warrants extensive longitudinal analyses of the recovery, phenotype and the functionality of the key immune effector cells after alloSCT in patients in relation to clinical outcome (relapse yes/no). Hereby, we aim to uncover the mechanisms that underly effective vs. dysfunctional graft-versus-tumor T and NK cell responses. These analyses include >35 parameter flow cytometry and advanced immunological assays. Together, the insights from these studies guide the subsequent development and exploration of strategies to further strengthen anti-tumor T and NK cell responses post alloSCT. These strategies include, dendritic cell (DC) vaccination, as DC are the key orchestrators of innate and adaptive immune responses, and adoptive transfer of NK cells. The last decade, we developed two unique and innovative ex vivo culture protocols to generate 1) high numbers of myeloid and plasmacytoid DCs and 2) highly potent NK cells from hematopoietic stem cells of the donor stem cell graft. Our DCs harbor exceptional NK and T cell stimulatory potential. In this project, we aim to further explore the optimal strategy and timing for post alloSCT DC vaccination and NK cell adoptive transfer in ex vivo and in vivo models.
For this project, we are looking for an ambitious PhD student. This four-year project should culminate in a PhD thesis. The PhD student will participate in the Radboudumc Graduate School and Radboud Research Program "Treatment Improvements for Severe Hematological Diseases".
Tasks and responsibilities
- Contribute to the acquisition of knowledge and new insights within the context of the department’s research program.
- Design and perform scientific research.
- Write scientific publications and present research data at scientific meetings and conferences.
- Work in a team with clinical and non-clinical PhD students and scientists.
- Discuss, plan and perform research in a stimulating environment.
- Work in an international research group.