This suggests that the initial direct blockade of HER3/PI3K/AKT/mTOR signaling in cancer cells plays a tumor inhibitory role at the beginning of CDX-3379 treatment, while the TIME remodeling activity of this HER3i may then stimulate adaptive anti-tumoral responses that are circumvented by CD8 T cell depletion. The gene discussed is CD8A; the disease is neoplasm.