Browsing by Author "Pine, Sharon R."

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    Engineered natural killer cells impede the immunometabolic CD73-adenosine axis in solid tumors
    (eLife Sciences, 2022-07-11) Chambers, Andrea M.; Lupo, Kyle B.; Wang, Jiao; Cao, Jingming; Utturkar, Sagar; Lanman, Nadia; Bernal-Crespo, Victor; Jalal, Shadia; Pine, Sharon R.; Torregrosa-Allen, Sandra; Elzey, Bennett D.; Matosevic, Sandro; Medicine, School of Medicine
    Immunometabolic reprogramming due to adenosine produced by CD73 (encoded by the 5'-ectonucleotidase gene NT5E) is a recognized immunosuppressive mechanism contributing to immune evasion in solid tumors. Adenosine is not only known to contribute to tumor progression, but it has specific roles in driving dysfunction of immune cells, including natural killer (NK) cells. Here, we engineered human NK cells to directly target the CD73-adenosine axis by blocking the enzymatic activity of CD73. In doing so, the engineered NK cells not only impaired adenosinergic metabolism driven by the hypoxic uptake of ATP by cancer cells in a model of non-small-cell lung cancer, but also mediated killing of tumor cells due to the specific recognition of overexpressed CD73. This resulted in a 'single agent' immunotherapy that combines antibody specificity, blockade of purinergic signaling, and killing of targets mediated by NK cells. We also showed that CD73-targeted NK cells are potent in vivo and result in tumor arrest, while promoting NK cell infiltration into CD73+ tumors and enhancing intratumoral activation.
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    Relationship between West African ancestry with lung cancer risk and survival in African Americans
    (SpringerLink, 2019-11) Mitchell, Khadijah A.; Shah, Ebony; Bowman, Elise D.; Zingone, Adriana; Nichols, Noah; Pine, Sharon R.; Kittles, Rick A.; Ryan, Bríd M.; Medical and Molecular Genetics, School of Medicine
    Purpose: African Americans, especially men, have a higher incidence of lung cancer compared with all other racial and ethnic groups in the US. Self-reported race is frequently used in genomic research studies to capture an individual's race or ethnicity. However, it is clear from studies of genetic admixture that human genetic variation does not segregate into the same biologically discrete categories as socially defined categories of race. Previous studies have suggested that the degree of West African ancestry among African Americans can contribute to cancer risk in this population, though few studies have addressed this question in lung cancer. Methods: Using a genetic ancestry panel of 100 SNPs, we estimated West African, European, and Native American ancestry in 1,407 self-described African Americans and 2,413 European Americans. Results: We found that increasing West African ancestry was associated with increased risk of lung cancer among African American men (ORQ5 vs Q1 = 2.55 (1.45-4.48), p = 0.001), while no association was observed in African American women (ORQ5 vs Q1 = 0.90 (0.51-1.59), p = 0.56). This relationship diminished following adjustment for income and education. Conclusions: Genetic ancestry is not a major contributor to lung cancer risk or survival disparities.