Gamma delta T cells in acute myeloid leukemia: biology and emerging therapeutic strategies.

γδ T cells play an important role in disease control in acute myeloid leukemia (AML) and have become an emerging area of therapeutic interest. These cells represent a minor population of T lymphocytes with intrinsic abilities to recognize antigens in a major histocompatibility complex-independent manner and functionally straddle the innate and adaptive immunity interface. AML shows high expression of phosphoantigens and UL-16 binding proteins that activate the Vδ2 and Vδ1 subtypes of γδ T cells, respectively, leading to γδ T cell-mediated cytotoxicity. Insights from murine models and clinical data in humans show improved overall survival, leukemia-free survival, reduced risk of relapse, enhanced graft-versus-leukemia effect, and decreased graft-versus-host disease in patients with AML who have higher reconstitution of γδ T cells following allogeneic hematopoietic stem cell transplantation. Clinical trials leveraging γδ T cell biology have used unmodified and modified allogeneic cells as well as bispecific engagers and monoclonal antibodies. In this review, we discuss γδ T cells' biology, roles in cancer and AML, and mechanisms of immune escape and antileukemia effect; we also discuss recent clinical advances related to γδ T cells in the field of AML therapeutics.

Mortality and Outcomes in Cerebrovascular Disease Patients With Emphasis on COVID-19: A Cross-Sectional Analysis of the National Inpatient Sample 2020.

Background COVID-19-related pulmonary complications have been explored extensively in the recent past. There is also a significant amount of literature on the neurological manifestations of COVID-19. However, there exists an unmet need to assess the impact of COVID-19 on patients with cerebrovascular diseases and its role in affecting mortality in such patients. Methods In this cross-sectional study, we analyzed 401,318 hospitalized patients with cerebrovascular diseases using the discharge data from the National Inpatient Sample 2020 to assess the association of COVID-19 with multiple clinical conditions, along with additional factors, such as length of stay in the hospital, total charges incurred, region and type of hospital, and primary insurance/payer in the United States of America. We used a multivariable logistic regression model to predict factors relating to mortality in such patients. Results The mortality during hospitalization in patients with cerebrovascular disease who were also diagnosed with COVID-19 was significantly higher than the patients without COVID-19 (22.50% vs 5.44%, p-value <0.0001). COVID-19 independently increased the odds of death significantly in patients with cerebrovascular diseases (adjusted OR = 4.81, p-value <0.0001). Other statistically and clinically significant factors that contributed to increased odds of mortality in such patients were comorbidities such as moderate/severe liver disease, myocardial infarction, congestive heart failure, and complications such as the development of a saddle pulmonary embolus. Conclusion COVID-19 was associated with higher mortality in patients with cerebrovascular diseases. It also significantly increased the duration of hospital stay and odds of mortality in such patients.