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Salvage therapy expands highly cytotoxic and metabolically fit resilient CD8+ T cells via ME1 upregulation.
- Source :
-
Science Advances . 11/17/2023, Vol. 9 Issue 46, p1-18. 18p. - Publication Year :
- 2023
-
Abstract
- Patients with advanced cancers who either do not experience initial response to or progress while on immune checkpoint inhibitors (ICIs) receive salvage radiotherapy to reduce tumor burden and tumor-related symptoms. Occasionally, some patients experience substantial global tumor regression with a rebound of cytotoxic CD8+ T cells. We have termed the rebound of cytotoxic CD8+ T cells in response to salvage therapy as T cell resilience and examined the underlying mechanisms of resilience. Resilient T cells are enriched for CX3CR1+ CD8+ T cells with low mitochondrial membrane potential, accumulate less reactive oxygen species (ROS), and express more malic enzyme 1 (ME1). ME1 overexpression enhanced the cytotoxicity and expansion of effector CD8+ T cells partially via the type I interferon pathway. ME1 also increased mitochondrial respiration while maintaining the redox state balance. ME1 increased the cytotoxicity of peripheral lymphocytes from patients with advanced cancers. Thus, preserved resilient T cells in patients rebound after salvage therapy and ME1 enhances their resiliency. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 23752548
- Volume :
- 9
- Issue :
- 46
- Database :
- Academic Search Index
- Journal :
- Science Advances
- Publication Type :
- Academic Journal
- Accession number :
- 173638838
- Full Text :
- https://doi.org/10.1126/sciadv.adi2414