Conversely, low concentrations of IFN-γ can enhance the properties of CTCs through the ICAM1/PI3K/AKT/NOTCH1 pathway, potentially contributing to tumor progression.457 Overall, the interplay between various immune cells and CTCs fosters an immunosuppressive TME that facilitates immune evasion, thereby leading to adaptive resistance against cancer immunotherapy. The gene discussed is PIK3CA; the disease is cancer.