Immunotherapies for cancer, such as immune checkpoint blockade or adoptive T-cell transfer, can lead to a long-lasting clinical response. But the therapeutic response rate remains low on account of many tumors that have evolved sophisticated strategies to evade immune surveillance. Solid tumors are characterized by the highly acidic microenvironment, which may weaken the effectiveness of antitumor immunity. Here, we explored a promising therapeutic development deployed by pH manipulation for avoiding immunoevasion. The highly acidified microenvironment of melanoma induces the expression of G-protein-coupled receptor (Ogr1) in T cells, which weakened their effective function and promote tumor growth. Ogr1 inhibition reactivate CD8+ T cells and have a cytotoxic role by reducing the activity of high glycolysis, resulting in comparatively low acidification of the tumor microenvironment, and leads to tumor suppression. In addition, the adoptive transfer of Ogr1−/−-CD8+ T cells enhanced the antitumor responses, with the potential for immediate clinical transformation.

BackgroundLung cancer frequently occurs in the clinic, leading to poor prognosis and high mortality. Markers for early diagnosis of lung cancer are scarce, and further potential therapeutic targets are also urgently needed.MethodWe established a new mouse model in which the specific gene HNRNPK (heterogeneous nuclear ribonucleoprotein K) was downregulated after administration of doxycycline. The lung metastatic nodules were investigated using bioluminescence imaging, micro‐CT, and autopsy quantification.ResultsCompared with the short hairpin negative control group, less lung metastatic nodules were formed in the short hairpin RNA group.ConclusionDownregulation of HNRNPK in cancer cells can inhibit lung metastasis.