Researchers at Stanford University School of Medicine have proposed a new approach to cancer immunotherapy that could solve one of the main challenges in treating solid tumors—the inability of immune cells to effectively penetrate the tumor. The study was published in *Nature Immunology*.

The method involves “equipping” immune cells with receptors capable of recognizing the byproducts of abnormal cancer cell metabolism. These substances spread through the intercellular space and act as chemical signals. As a result, modified immune cells begin moving toward the tumor like “trackers” following a scent.

This approach differs from classical CAR-T therapy, where immune cells target proteins on the tumor surface. In the new method, they respond to small molecules—metabolites released by cancer cells. This allows them not only to detect tumors but also to penetrate them more effectively.

The scientists used CRISPR gene editing to activate hundreds of genes in natural killer (NK) cells and identify which ones enhance migration into tumors. They discovered a special class of receptors—so-called thGPRs—that respond to lipids, fatty acids, and cholesterol derivatives actively produced by cancer cells.

One key receptor, GPR183, showed particularly impressive results. Immune cells engineered to express it were significantly better at locating and infiltrating tumors. In experiments on mice with human breast and ovarian tumors, this led to markedly improved tumor control and survival. In some cases, aggressive tumors disappeared completely and did not return.

The authors emphasize that the challenge of immunotherapy for solid tumors lies not only in T-cell “exhaustion” but also in spatial factors—too few immune cells actually reach the tumor. The new approach effectively turns the metabolic features of cancer, previously seen merely as signs of aggressiveness, into tools for its detection and destruction.

Researchers are now preparing for clinical trials and exploring ways to expand the method—for example, using metabolites not only as “beacons” but also as activation signals for immune cells directly within tumors.