Preclinical Combo Reprograms Tumor Immunity to Overcome Colorectal Cancer Resistance

Overview

• Mount Sinai researchers report in Cell Reports Medicine that restoring coordination between T cells and macrophages let the immune system clear colorectal tumors in preclinical models.
• The most effective regimen blocked three T‑cell checkpoints—PD‑1, CTLA‑4, and LAG3—while targeting TREM2, a marker on macrophages that shut down T‑cell attack.
• In models, the approach achieved up to 100% complete responses in mismatch repair–deficient tumors and more than 70% in mismatch repair–proficient tumors, which rarely respond to single‑drug immunotherapy.
• Animals that cleared their tumors resisted a later tumor re‑challenge, showing immune memory that could translate into longer‑lasting protection.
• Single‑cell and spatial analyses traced resistance to exhausted T cells and suppressive macrophages, and the team says the results justify rational combination trials, with safety and dosing to be tested in patients.