IMPROVING DIVERSE PARTICIPATION IN CANCER CLINICAL TRIALS.

Despite significant improvement in overall cancer mortality (>30% since 1991), these survival benefits have not been experienced by all groups uniformly especially in those of diverse heritage. Drivers of cancer health inequity are multi-factorial including more adverse social determinants of health, later stage cancer presentation, decreased health care access, decreased health literacy, and cultural barriers to prompt cancer care. Adding to these disparities is the historical inclusion of primarily well-insured Caucasian patients into cancer clinical trials leading to deep gaps in understanding both the efficacy and safety of new therapies in the actual populations for which these medications will be used. The need for trial accruals to reflect the U.S. population (i.e., diverse) is essential across diseases, but especially those in which certain minority populations are overrepresented (Latinos and hepatocellular carcinoma, African Americans and myeloma and prostate cancer). Strategies and new legislation to increase diversity in trial accruals are outlined and discussed.

Alloantigen Infusion Activates the Transcriptome of Type 2 Conventional Dendritic Cells.

Recent studies have revealed novel molecular mechanisms by which innate monocytic cells acutely recognize and respond to alloantigen with significance to allograft rejection and tolerance. What remains unclear is the single-cell heterogeneity of the innate alloresponse, particularly the contribution of dendritic cell (DC) subsets. To investigate the response of these cells to exposure of alloantigen, C57BL/6J mice were administered live allogenic BALB/cJ splenic murine cells versus isogenic cells. In parallel, we infused apoptotic allogenic and isogenic cells, which have been reported to modulate immunity. Forty-eight hours after injection, recipient spleens were harvested, enriched for DCs, and subjected to single-cell mRNA sequencing. Injection of live cells induced a greater transcriptional change across DC subsets compared with apoptotic cells. In the setting of live cell infusion, type 2 conventional DCs (cDC2s) were most transcriptionally responsive with a Ccr2+ cDC2 subcluster uniquely responding to the presence of alloantigen compared with the isogenic control. In vitro experimentation confirmed unique activation of CCR2+ cDC2s following alloantigen exposure. Candidate receptors of allorecognition in other innate populations were interrogated and A type paired Ig-like receptors were found to be increased in the cDC2 population following alloexposure. These results illuminate previously unclear distinctions between therapeutic infusions of live versus apoptotic allogenic cells and suggest a role for cDC2s in innate allorecognition. More critically, these studies allow for future interrogation of the transcriptional response of immune cells in the setting of alloantigen exposure in vivo, encouraging assessment of novel pathways and previously unexamined receptors in this setting.

Emerging Roles for Dendritic Cells in Heart Failure.

The field of cardio-immunology has emerged from discoveries that define roles for innate and adaptive immune responses associated with myocardial inflammation and heart failure. Dendritic cells (DCs) comprise an important cellular compartment that contributes to systemic immune surveillance at the junction of innate and adaptive immunity. Once described as a singular immune subset, we now appreciate that DCs consist of a heterogeneous pool of subpopulations, each with distinct effector functions that can uniquely regulate the acute and chronic inflammatory response. Nevertheless, the cardiovascular-specific context involving DCs in negotiating the biological response to myocardial injury is not well understood. Herein, we review our current understanding of the role of DCs in cardiac inflammation and heart failure, including gaps in knowledge and clinical relevance.

Practice Transformation to Improve Cancer Screening Outcomes at an Academic Medical Center.

In 2011, Texas received federal approval of the 1115 Healthcare Transformation waiver, which went to support the Texas Delivery System Reform Incentive Payment Program (DSRIP) incentivizing the transformation of service delivery practices which included expanded coverage of preventive cancer screenings. There is limited evidence that quality improvement initiatives stemming from DSRIP improve cancer screening outcomes for the Medicaid, low-income, and uninsured (MLIU) patient population. The present the results of a quality initiative to improve breast, cervical, and colorectal cancer screening rates for MLIU patients receiving primary care at an academic medical center. The initiative included engaging multidisciplinary primary care teams, health information technology (IT), and quality departments to standardize workflows. We found significantly improved rates of cervical and colorectal cancer screening among patients eligible to receive one or more screenings. Aligning primary care, IT, and quality processes resulted in significant improvement in cancer screening.