This research identifies ADAM12 as a critical molecular checkpoint in cancer-associated fibroblasts (CAFs) that actively prevents the immune system from attacking tumors. Using advanced CRISPR-based single-cell screening on patient tissues, scientists discovered that ADAM12 maintains a pro-tumor environment by fueling TGF-β signaling and suppressing beneficial interferon responses. When ADAM12 is removed, fibroblasts shift from a restrictive "cold" state to a progenitor-like state that permits CD8+ T cell infiltration. This cellular reprogramming successfully shrinks tumors and significantly boosts the effectiveness of immunotherapy in various preclinical models. Because ADAM12 is primarily found in tumors rather than healthy tissue, it represents a highly promising and precise therapeutic target for treating solid cancers.

References:

• Li J, Liu H, Guo Q, et al. Single-cell screens identify ADAM12 as a fibroblast checkpoint impeding anti-tumor immunity[J]. Cancer Cell, 2026.