Here, we adopted the HA hydrogel with optimized stiffness and pore size for TRM-like cell delivery, termed TRM-like cell–encapsulated hydrogel (TRM-EH) (Fig. 1), to drive effective local and systemic antitumor immune responses in mouse colon carcinoma and melanoma models and explored the synergistic effect of TRM-EH with a programmed cell death protein 1 (PD-1) blocking antibody. This evidence concerns the gene PDCD1 and melanoma.