SHP-2 and PD-1-SHP-2 signaling regulate myeloid cell differentiation and antitumor responses.

The inhibitory receptor PD-1 suppresses T cell activation by recruiting the phosphatase SHP-2. However, mice with a T-cell-specific deletion of SHP-2 do not have improved antitumor immunity. Here we showed that mice with conditional targeting of SHP-2 in myeloid cells, but not in T cells, had diminished tumor growth.

Commentary on: Combination of Metabolic Intervention and T Cell Therapy Enhances Solid Tumor Immunotherapy.

Metabolism is a common cellular feature. Cancer creates a suppressive microenvironment resulting in inactivation of antigen-specific T cells by metabolic reprogramming. Development of approaches that enhance and sustain physiologic properties of T cell metabolism to prevent T cell inactivation and promote effector function in the tumor microenvironment is an urgent need for improvement of cell-based cancer immunotherapies.

T Cell Metabolism in Cancer Immunotherapy.

Immune checkpoint therapies aiming to enhance T cell responses have revolutionized cancer immunotherapy. However, although a small fraction of patients develops durable anti-tumor responses, the majority of patients display only transient responses, underlying the need for finding auxiliary approaches. Tumor microenvironment poses a major metabolic barrier to efficient anti-tumor T cell activity.

Targeted deletion of PD-1 in myeloid cells induces antitumor immunity.

PD-1, a T cell checkpoint receptor and target of cancer immunotherapy, is also expressed on myeloid cells. The role of myeloid-specific versus T cell-specific PD-1 ablation on antitumor immunity has remained unclear because most studies have used either PD-1-blocking antibodies or complete PD-1 KO mice. We generated a conditional allele, which allowed myeloid-specific (PD-1) or T cell-specific (PD-1) targeting of gene.

Reactivation of BK virus after double umbilical cord blood transplantation in adults correlates with impaired reconstitution of CD4 and CD8 T effector memory cells and increase of T regulatory cells.

BK virus (BKV), a human polyomavirus that remains latent in renal epithelial cells, can be reactivated after hematopoietic stem cell transplantation (HSCT) leading to hemorrhagic cystitis. The incidence of BK viremia is higher after Umbilical cord blood transplantation (UCBT) than HSCT from adult donors. Data regarding the role of immune recovery after UCBT in BKV reactivation is lacking.

Metabolic Targets for Improvement of Allogeneic Hematopoietic Stem Cell Transplantation and Graft-vs.-Host Disease.

Utilization of the adaptive immune system against malignancies, both by immune-based therapies to activate T cells to attack cancer and by T-cell therapies to transfer effector cytolytic T lymphocytes (CTL) to the cancer patient, represent major novel therapeutic advancements in oncologic therapy. Allogeneic hematopoietic stem cell (HSC) transplantation (HSCT) is a form of cell-based therapy, which replaces the HSC in the patient's bone marrow but also serves as a T-cell therapy due to the Graft-vs.-leukemia (GVL) effect mediated by donor T cells transferred with the graft.