Dana‑Farber investigators identified interferon‑gamma signaling within tumor‑associated myeloid cells as a driver of resistance to immune checkpoint inhibitors in advanced renal cell carcinoma. The study showed that myeloid IFNγ pathways reprogram the tumor microenvironment and blunt T‑cell activity, pointing to myeloid signaling as a potential therapeutic target. At UCLA, researchers found that DNA copy‑number alterations in melanoma shape resistance to checkpoint blockade and highlighted candidate genomic lesions that correlate with therapeutic failure. Both studies combine translational profiling and functional work to nominate biomarkers and new combination strategies. Collectively, these mechanistic insights suggest targeting myeloid compartments and addressing tumor genomic adaptations may be required to overcome primary and acquired immunotherapy resistance in solid tumors.