Publications by authors named "B J Oswald"
Exhausted T cells (TEX) in cancer and chronic viral infections undergo metabolic and epigenetic remodeling, impairing their protective capabilities. However, the impact of nutrient metabolism on epigenetic modifications that control TEX differentiation remains unclear. We showed that TEX cells shifted from acetate to citrate metabolism by downregulating acetyl-CoA synthetase 2 (ACSS2) while maintaining ATP-citrate lyase (ACLY) activity.
View Article and Find Full Text PDFReducing calorie intake without malnutrition limits tumor progression but the underlying mechanisms are poorly understood. Here we show that dietary restriction (DR) suppresses tumor growth by enhancing CD8 T cell-mediated anti-tumor immunity. DR reshapes CD8 T cell differentiation within the tumor microenvironment (TME), promoting the development of effector T cell subsets while limiting the accumulation of exhausted T (Tex) cells, and synergizes with anti-PD1 immunotherapy to restrict tumor growth.
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- The COVID-19 pandemic revealed health disparities in underserved Latino/a communities, particularly regarding testing access.
- The CO-CREATE project developed a community-driven, culturally-tailored COVID-19 testing program in San Ysidro in partnership with local health organizations.
- Over two years, the program provided 24,422 tests to a primarily Latino/a population, significantly enhancing testing rates and emphasizing the need for future public health strategies to improve access for underserved communities.
Glucose is essential for T cell proliferation and function, yet its specific metabolic roles remain poorly defined. Here, we identify glycosphingolipid (GSL) biosynthesis as a key pathway fueled by glucose that enables CD8 T cell expansion and cytotoxic function . Using C-based stable isotope tracing, we demonstrate that CD8 effector T cells use glucose to synthesize uridine diphosphate-glucose (UDP-Glc), a precursor for glycogen, glycan, and GSL biosynthesis.
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- Coordination of cellular metabolism is crucial for effective CD8 T cell responses during infections, highlighting the role of cytosolic acetyl-CoA production.
- The enzyme ATP citrate lyase (ACLY) is responsible for generating acetyl-CoA from citrate, and its absence leads T cells to rely on an alternative pathway involving acyl-CoA synthetase short-chain family member 2 (ACSS2) which uses acetate.
- Both ACLY and ACSS2 are important for managing acetyl-CoA levels, impacting T cell function through modifications like histone acetylation and chromatin accessibility at key effector gene sites.