Allo-HCT is a curative-intent therapy of numerous hematological malignancies. Despite advances in the field, the broader implementation of allo-HCT is limited by high rates of transplant-related complications, with 3-year overall mortality approaching 50% (41). The goal of my postdoctoral projects was to study immune reconstitution after allo-HCT, factors influencing the reconstitution of specific immune cell subsets and strategies to improve immune reconstitution and diminish the risk of relapse. In Aim 1, I was able to demonstrate a novel link between early post-transplantation gut microbiome and its metabolic activity and MAIT and Vd2 cell populations. I was also able to link their early reconstitution to a positive effect on allo-HCT outcomes, especially the GVHD development. Although the mechanism of protection remains not completely clear, I speculate that the upregulation of the proinflammatory and cytotoxic genes in microbiota-responsive populations could reflect a role for these populations in controlling pathogenenic bateria or cell populations. In Aim 2, I was able to demonstrate that genetic modification of precursor T cells with orthogonal interleukin 7 receptor and their consecutive stimulation with the corresponding orthogonal cytokine in vivo leads to improved thymic reconstitution early post-transplantation and higher CD4 and CD8 proportions in the lymph nodes compared to the precursor T cells without stimulation. I also showed that precursor T cells can be transduced with a CAR construct and migrate to the thymus when the CAR is not signaling. Further experiments are needed to develop genetically modified precursor T cells into a more potent booster of post-transplantation T cell immunity and mature, donor unrestricted CAR T cells fighting possible relapse after allo-HCT. I feel that my research has helped to gain some additional understanding of immune reconstitution and function and the factors influencing these processed, such as gut microbiome. I have also had a deeper insight in developing new cellular therapies to improve immune reconstitution and anti-tumor responses. I have extended my postdoctoral time in the van den Brink lab and am currently still working on the Aim 2 of the proposal.