CD26lowPD-1+ CD8 T cells are terminally exhausted and associated with leukemia progression in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a devastating blood cancer with poor prognosis. Novel effective treatment is an urgent unmet need. Immunotherapy targeting T cell exhaustion by blocking inhibitory pathways, such as PD-1, is promising in cancer treatment. However, results from clinical studies applying PD-1 blockade to AML patients are largely disappointing. AML is highly heterogeneous. Identification of additional immune regulatory pathways and defining predictive biomarkers for treatment response are crucial to optimize the strategy. CD26 is a marker of T cell activation and involved in multiple immune processes. Here, we performed comprehensive phenotypic and functional analyses on the blood samples collected from AML patients and discovered that CD26lowPD-1+ CD8 T cells were associated with AML progression. Specifically, the percentage of this cell fraction was significantly higher in patients with newly diagnosed AML compared to that in patients achieved completed remission or healthy controls. Our subsequent studies on CD26lowPD-1+ CD8 T cells from AML patients at initial diagnosis demonstrated that this cell population highly expressed inhibitory receptors and displayed impaired cytokine production, indicating an exhaustion status. Importantly, CD26lowPD-1+ CD8 T cells carried features of terminal exhaustion, manifested by higher frequency of TEMRA differentiation, increased expression of transcription factors that are observed in terminally exhausted T cells, and high level of intracellular expression of granzyme B and perforin. Our findings suggest a prognostic and predictive value of CD26 in AML, providing pivotal information to optimize the immunotherapy for this devastating cancer.

Post-transplant cyclophosphamide alters immune signatures and leads to impaired T cell reconstitution in allogeneic hematopoietic stem cell transplant.

Despite the increased usage of post-transplant cyclophosphamide (PTCy) in allogeneic hematopoietic stem cell transplantation (allo-HSCT), our knowledge of immune reconstitution post-allo-HSCT in the setting of PTCy is limited. Adequate immune reconstitution is the key to a successful transplant. In this study, we aim to investigate the effect of PTCy on the reconstitution of each immune component; more focus was placed on the immunophenotype and functions of T cells. Using blood samples from patients who underwent allo-HSCT under regimens containing PTCy (n = 23) versus those who received no PTCy (n = 14), we examined the impact of PTCy on the post-transplant immune response. We demonstrated a distinct T cell immune signature between PTCy versus non-PTCy group. PTCy significantly delayed T cell reconstitution and affected the T cell subsets by increasing regulatory T cells (Treg) while reducing naïve T cells. In addition, we observed remarkable enhancement of multiple inhibitory receptors (TIGIT, PD-1, TIM-3, CD38, CD39) on both CD4+ and CD8+ T cells on day 30 post-transplantation in patients who received PTCy. Importantly, upregulation of PD-1 on CD8 T cells was persistent through day 180 and these T cells were less functional, manifested by reduced cytokine production upon anti-CD3/CD28 stimulation. Furthermore, we found a significant correlation of T cell immune phenotypes to clinical outcome (disease relapse and GVHD) in patients who received PTCy. Our novel findings provide critical information to understand the mechanism of how PTCy impacts immune reconstitution in allo-HSCT and may subsequently lead to optimization of our clinical practice using this treatment.

ASFA Category IV becomes Category I: Idiopathic thrombotic thrombocytopenic purpura in a patient with presumed gemcitabine-induced thrombotic microangiopathy.

In the implementation of American Society for Apheresis national guidelines, the decision for therapeutic plasma exchange may be confounded by a clinical presentation that fits both a Category I and IV designation. We report the case of a 45-year-old female who presented with concern for a Category IV disorder, gemcitabine-induced thrombotic microangiopathy, and was ultimately diagnosed with a Category I disorder, idiopathic thrombotic thrombocytopenic purpura. This case highlights the importance of ruling out idiopathic TTP by a thorough evaluation for ADAMTS13 activity and inhibitor, even when an alternate thrombotic microangiopathy diagnosis may be likely.

Discussing the Evidence for Upstream Palliative Care in Improving Outcomes in Advanced Cancer.

Palliative care has received increasing attention at the American Society of Clinical Oncology (ASCO) Annual Meeting since the publication of its provisional clinical opinion on the topic in 2012. Despite frequent discussion, palliative care remains a source of some controversy and confusion in clinical practice, especially concerning who should provide it, what it encompasses, and when and how it can help patients and their families. In this article, we provide a formal definition of palliative care and review the state of the science of palliative care in oncology. Several randomized controlled trials now show that palliative care improves important outcomes for patients with cancer. Related outcome improvements include a reduction in symptoms, improved quality of life, better prognostic understanding, less depressed mood, less aggressive end-of-life care, reduced resource utilization, and even prolonged survival. As such, ASCO recommends early integration of palliative care into comprehensive cancer care for all patients with advanced disease and/or significant symptom burden. Our aim is that this summary will facilitate greater understanding about palliative care and encourage further integration of palliative care services into cancer care. More research is needed to illuminate the mechanisms of action of palliative care and to improve the specificity of palliative care applications to unique scenarios and populations in oncology.