Lactic acid is a metabolic checkpoint for Treg cells (from Jynto via Wikimedia Commons)

The intratumoral ratio of CD8+ T cells to regulatory T (Treg) cells impacts responsiveness to PD-1 blockade. Kumagai et al. find the ratio of CD8+ T cells to Treg cells is low in highly glycolytic tumors, including MYC-amplified tumors and liver metastases, and that expression of PD-1 is lower in CD8+ T cells than Treg cells. This effect is mediated by tumor-derived lactic acid and leads to resistance to PD-1 blockade in mouse models of Myc-overexpressing colon cancer and intrahepatic tumors. Blocking lactic-acid production or its uptake by Treg cells overcomes this resistance, suggesting potential new targets for cancer immunotherapy.

Kumagai S, , Nishikawa H.Cancer Cell2022 Feb 14;40:201–18.e9.

Pancreatic cancer can be protected from CAR T cells by N-glycans (from Neelima Shah and Edna Cukierman via NCI Visuals...

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