MUSC Hollings Cancer Center

Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition whose clinical severity may be influenced by social factors. We aimed to identify distinct COPD clinical phenotypes and assess variation by social determinants of health. In this retrospective cohort study, we identified adults aged 50-80 years with a diagnosis of COPD (n=59 797) at a tertiary academic medical centre in North-Central Florida using codes from International Classification of Diseases. Latent class analysis defined COPD clinical phenotypes using indicators of clinical severity, including frequency of acute care encounters (urgent care, emergency department visits and hospitalisations), presence of COPD as the principal diagnosis, comorbidity burden and use of Global Initiative for Chronic Obstructive Lung Disease Group D medications. Kaplan-Meier survival curves and Cox proportional hazards models assessed mortality across phenotypes. Multinomial logistic regression models estimated associations between phenotype membership and race/ethnicity, income, rurality and smoking status, using the minimal phenotype as reference. Five clinical phenotypes were identified: minimal (20.9%), mild (35.2%), moderate (22.5%), severe (12.2%) and very severe (9.3%). The very severe phenotype had the highest mortality (adjusted HR 2.94; 95% CI 2.72 to 3.18). Odds of very severe COPD were higher among non-Hispanic Black (adjusted OR (aOR) 1.29; 95% CI 1.21 to 1.36) and Hispanic individuals (aOR 1.75; 95% CI 1.63 to 1.87), those in the lowest income communities (aOR 1.25; 95% CI 1.18 to 1.32), rural residents (aOR 1.80; 95% CI 1.68 to 1.92) and individuals who currently smoke (aOR 1.30; 95% CI 1.20 to 1.42). Most patients with COPD had mild disease; however, the very severe phenotype, which was associated with higher mortality, was more common among Black and Hispanic individuals, those residing in lower-income and rural areas and those who currently smoke. These clinical phenotypes highlight sociodemographic differences in COPD severity as reflected in healthcare utilisation and outcomes.

Abstract Description Immunosuppressive myeloid populations, like myeloid-derived suppressor cells (MDSCs), within the tumor microenvironment (TME), hinder cancer immunotherapy. Targeting this suppression is vital to enhance anti-tumor T cell function in the TME. Our research shows that inhibiting SphK2-mediated S1P generation in MDSCs reshapes the TME, promoting tumor control. In preclinical checkpoint-resistant breast, bladder, and melanoma cancer models, SphK2 inhibition sensitizes tumors to anti-PD1 therapy, reducing tumor growth by alleviating MDSC suppression. Mechanistically, the MS-based proteomics analysis revealed that S1P interacts with Acetyl CoA carboxylase isoforms (ACC1 and ACC2), key enzymes in fatty acid metabolism. Enhancing ACC1/2 activity reprograms MDSC metabolism by increasing glycolysis through elevated Pyruvate Kinase M2 activity while reducing fatty acid oxidation. This metabolic shift promotes an immunogenic MDSC phenotype, enhancing antigen presentation to T cells. Moreover, lipidomic analysis showed that altered ACC1/2 activity increases fatty acid synthesis, particularly phosphatidylcholine (PC). Notably, PC supplementation alleviates ER stress in tumor-associated MDSCs, a key driver of their suppressive function. These findings establish S1P as a critical immunoregulatory mediator and PC as an immunostimulatory molecule, highlighting the SphK2/ACC/phospholipid axis as a promising target to counteract immunosuppression and enhance the efficacy of cancer immunotherapy. Funding Sources Department of Surgery, MUSC, Swim Across America foundation (SAA) NCI R01 CA250458, R01 CA236379 Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)

Tobacco use is the primary contributor to disease and death in the United States, and cigarette smoking is the leading risk factor for lung cancer. Safe and effective treatments for tobacco dependence exist; however, access to and use of tobacco treatment remains low. The most recent Centers for Medicare and Medicaid Services National Coverage Determination requires a shared decision-making visit for lung cancer screening that includes counseling on the importance of maintaining cigarette smoking abstinence if a person formerly smoked; or the importance of smoking cessation if a person currently smokes and, if appropriate, furnishing of information about tobacco-cessation interventions. The directive is not well defined and provides little guidance for delivering high-quality cessation services. Effective integration of best practices for tobacco treatment in the context of lung cancer screening must extend far beyond recommendations to quit, patient literature to reinforce quitting, and available evidence-based treatments. To optimize the provision of tobacco treatment and improve health outcomes in people being screened for lung cancer, the American Cancer Society National Lung Cancer Roundtable Tobacco Treatment in the Context of Lung Cancer Screening Task Group recommends: (1) specify quality indicators and document tobacco treatment delivery; (2) embed tobacco treatment in lung cancer screening; (3) advocate for increased access to tobacco treatment; (4) build and train lung cancer screening staff; (5) provide full coverage of treatment medications; (6) leverage electronic health records to improve the provision of cessation services to lung cancer screenees; and (7) identify and address contextual barriers to incorporating tobacco treatment guidelines in screening.