Tricking the Trickster: Precision Medicine Approaches to Counteract Leukemia Immune Escape after Transplant

Over the last decades, significant improvements in reducing the toxicities of allogeneic hematopoietic cell transplantation (allo-HCT) have widened its use as consolidation or salvage therapy for high-risk hematological malignancies. Nevertheless, relapse of the original malignant disease remains an open issue, with unsatisfactory salvage options and limited rationales to select amongst them. In the last years, a number of studies have highlighted that relapse is often associated to specific genomic and non-genomic mechanisms of immune escape. In the present review, we will summarize current knowledge about these modalities of immune evasion, focusing in particular on mechanisms that leverage on antigen presentation and on pathologic rewiring of the bone marrow microenvironment. We will present examples of how this biological information can be translated into specific approaches to treat relapse, discuss the status of the clinical trials for patients who relapsed after transplant, and show how dissecting the complex immunobiology of allo-HCT represents a crucial step to develop new personalized approaches to improve clinical outcomes.