Taking out macrophages allows the immune system to target tumors

According to findings published earlier this month in Cancer Immunology Research, researchers from the Icahn School of Medicine at Mount Sinai report a new means of counteracting therapeutic resistance in cancer cells: Take out their goons. Chimeric antigen receptor (CAR) T cells can be made to target the tumor-associated macrophages that protect cancer cells from the rest of the immune system.

CAR T cells have been used to treat cancer before, but always by targeting the cancer cells themselves. Here, researchers found that targeting TAMs instead could produce an even more pronounced effect. TAMs usually infiltrate the tumor and physically block the channels that immune cells would otherwise use to enter and attack it. By taking out the TAMs, the CAR T cells allows the rest of the immune system to bring its weight to bear.

“Our initial goal was just to use the CAR T cells to kill the immunosuppressive macrophages, but we discovered they were also boosting tumor immunity by releasing this powerful immune-boosting molecule,” said study co-author Brian Brown. Dr. Brown is Director of the Icahn Genomics Institute.

Another co-author, Dr. Miriam Merad, pointed out that this new technique addresses a perennial problem in cancer treatment: “Our molecular studies of human tumors have revealed macrophage subsets present in human tumors and not in normal tissues and are similar across tumors and across patients. So macrophage-targeting CAR T cells could be a broad way to target different types of solid tumors and improve immunotherapy.”

The research team tested this process in an in vitro model of lung cancer and in vivo mouse models of lung, pancreatic, and ovarian tumors. In all cases, the CAR T cells infiltrated the lesions, blockaded PD-1, and destroyed TAMs without any toxic side effects.

Sánchez-Paulete A, Mateus-Tique J, Mollaoglu G, Nielsen S, Marks A, Lakshmi A, et al.; Targeting Macrophages with CAR T Cells Delays Solid Tumor Progression and Enhances Antitumor Immunity. Cancer Immunol Res 2022; doi: 10.1158/2326-6066.CIR-21-1075