In summary, our data clearly demonstrate that in contrast to respective monotherapies, HER2-targeted NK-92/5.28.z CAR-NK cells applied in combination with anti-PD-1 checkpoint inhibition efficiently induces tumor regression of advanced tumors in the immunocompetent GL261/HER2 mouse model, accompanied by alterations in the glioma-specific tumor microenvironment consistent with a switch from an immunologically “cold” to an immunologically more accessible tumor. Here, ERBB2 is linked to neoplasm.