CD8+ T cells pass the acid test

Oh, Ju Hee; Archambault, Anne-Sophie; Geltink, Ramon I. Klein

doi:10.1038/s42255-023-00738-6

Cited by 1 publication

(1 citation statement)

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“…The maintenance of a reversed pH gradient via solute carrier family 4 member 4 (SLC4A4) expression is essential for glycolysis-dependent lactate production and immune evasion in PDAC (Cappellesso et al, 2022). Conversely, acid exposure inhibits the BHLH transcription factor (MYC)-solute carrier family 7 member 5 (SLC7A5) axis in T cells, leading to impaired methionine uptake, reprogramming of onecarbon metabolism and epigenetic landscape, and ultimately promoting mitochondrial metabolic adaptivity and quiescence (Cheng et al, 2023;Oh et al, 2023). These potential targets further pave the way for possible therapeutic strategies targeting alkaliptosis to overcome resistance to immunotherapy.…”

Section: The Atp6v0d1-stat3 Pathwaymentioning

confidence: 99%

Mechanisms of alkaliptosis

Chen

Kang

Liu

et al. 2023

Front. Cell Dev. Biol.

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Malignant tumors represent a major threat to global health and the search for effective treatments is imperative. While various treatments exist, including surgery, radiotherapy, chemotherapy, immunotherapy and combination therapies, there remains a need to develop therapies that target regulated cell death pathways to eliminate cancer cells while preserving normal cells. Alkaliptosis, a pH-dependent cell death process triggered by the small molecular compound JTC801, has been identified as a novel approach for malignant tumor treatment, particularly in pancreatic cancer. Two major signaling pathways, the NF-κB-CA9 pathway and the ATP6V0D1-STAT3 pathway, contribute to the induction of alkaliptosis. This review summarizes recent developments in our understanding of alkaliptosis signals, mechanisms, and modulation, and explores its context-dependent effects on drug resistance, inflammation, and immunity. By providing a deeper understanding of the heterogeneity and plasticity of cell death mechanisms, this information holds promise for informing the design of more effective anti-tumor therapies.

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Section: The Atp6v0d1-stat3 Pathwaymentioning

confidence: 99%