ABSTRACT
This JAMA Patient Page describes Lynch syndrome, its risk factors and diagnosis, and its association with colorectal cancer and other specific cancers.
Subject(s)
Colorectal Neoplasms, Hereditary Nonpolyposis , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis , HumansABSTRACT
African American/Black (henceforth Black) men face disproportionate risks of morbidity and mortality from both cardiovascular disease (CVD) and colorectal cancer (CRC). The American Heart Association's Life's Simple 7 (LS7) tool was designed to examine predictors of CVD with included behaviors also linked to CRC risk (i.e., smoking status, weight, diet, and physical activity). However, no studies have combined LS7 assessment alongside CRC screening history, which serves as a proxy for assessing CRC risk, in Black men. In this study, Black men aged 45-75 participating in annual community wellness events were screened for 6 of 7 LS7 measures (excluding diet, LS6) and self-reported CRC screening. Analyses conducted using R 4.0.5. revealed that Black men (N = 680), with an average age of 57.3 years (SD = 7.5), reported poor (39.7%), intermediate (34.6%), or ideal (25.7%) LS6 scores with higher scores corresponding to lower risk for CVD. However, for every 1-point increase in LS6 scores (0-6), there was a 26% lower odds of reported CRC screening (p = .001). In the fully adjusted model, men with 4+ ideal LS6 behaviors had a 60% lower odds of self-reported CRC screening compared to those with two ideal LS6 behaviors (p < .001). These findings underscore the need for culturally relevant interventions for Black men across all levels of cardiovascular health (CVH) to increase CRC screening uptake.
Subject(s)
Black or African American , Cardiovascular Diseases , Colorectal Neoplasms , Early Detection of Cancer , Humans , Male , Middle Aged , Colorectal Neoplasms/diagnosis , Cross-Sectional Studies , Black or African American/statistics & numerical data , Aged , United States , Mass ScreeningABSTRACT
Mantle cell lymphoma (MCL) is an aggressive B-cell malignancy for which novel therapeutics with improved efficacy are greatly needed. To provide support for clinical immune checkpoint blockade, we comprehensively evaluated the expression of therapeutically targetable immune checkpoint molecules on primary MCL cells. MCL cells showed constitutive expression of Programmed Death 1 (PD-1) and Programmed Death Ligand 1 (PD-L1), variable CD200, absent PD-L2, Lymphocyte Activation Gene 3 (LAG-3), and Cytotoxic T-cell Associated Protein 4 (CTLA-4). Effector cells from MCL patients expressed PD-1. Co-culture of MCL cells with T-cells induced PD-L1 surface expression, a phenomenon regulated by IFNγ and CD40:CD40L interaction. Induction of PD-L1 was attenuated by concurrent treatment with ibrutinib or duvelisib, suggesting BTK and PI3K are important mediators of PD-L1 expression. Overall, our data provide further insight into the expression of checkpoint molecules in MCL and support the use of PD-L1 blocking antibodies in MCL patients.
