Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0847097 (
acidity
)
15,165
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Clinical data from diverse cancer types shows that the increased T cell infiltration in tumors correlates with improved patient prognosis. Acidic extracellular pH is a major attribute of the tumor microenvironment (TME) that promotes immune evasion and tumor progression. Therefore, antagonizing tumor
acidity
can be a powerful approach in cancer immunotherapy. Here, Pluronic F-127 is used as a NaHCO
3
releasing carrier to focally alleviate extracellular tumor
acidity
. In a mouse tumor model, intratumoral treatment with pH modulating injectable gel (pH
e
-MIG) generates immune-favorable TME, as evidenced by the decrease of immune-suppressive cells and increase of tumor infiltrating CD8+T cells. The combination of pH
e
-MIG with immune checkpoint inhibitors, anti-PD-1 and anti-
TIGIT
antibodies, increases intratumoral T cell function, which leads to tumor clearance. Mechanistically, extracellular
acidity
was shown to upregulate co-inhibitory immune checkpoint receptors and inhibit mTOR signaling pathways in memory CD8+T cells, which impaired effector functions. Furthermore, an acidic pH environment increased the expression and engagement of
TIGIT
and its ligand CD155, which suggested that the extracellular pH can regulate the suppressive function of
TIGIT
pathway. Collectively, these findings suggest that pH
e
-MIG holds potential as a new TME modulator for effective immune checkpoint inhibitor therapies.
...
PMID:Extracellular pH modulating injectable gel for enhancing immune checkpoint inhibitor therapy. 3166 64
