Targeted therapy against the programmed cell death ligand-1 (PD-L1) blockade holds considerable promise for the treatment of different tumor types; however, little effect has been observed against gliomas thus far. Effective glioma therapy requires a delivery vehicle that can reach tumor cells in the central nervous system, with limited systemic side effect. In this study, we developed a cyclic peptide iRGD (CCRGDKGPDC)-conjugated solid lipid nanoparticle (SLN) to deliver small interfering RNAs (siRNAs) against both epidermal growth factor receptor (EGFR) and PD-L1 for combined targeted and immunotherapy against glioblastoma, the most aggressive type of brain *

SUMMARY CD8 + tissue-resident memory T cells (T RM ) persist at sites of previous infection, where they provide rapid local protection against pathogen challenge. CD8 + T RM expressing the α1 chain (CD49a) of integrin VLA-1 have been identified within sites of resolved skin infection and in vitiligo lesions. We demonstrate that CD49a is expressed early following T cell activation in vivo, and TGF-β and IL-12 induce CD49a expression by CD8 + T cells in vitro. Despite this rapid expression, CD49a is not required for the generation of a primary CD8 + T cell response to cutaneous herpes simplex virus (HSV) infection, migration of CD8 + T cells across the epidermal basement membrane, or positioning of T RM within basal epidermis. Rather, CD49a supports CD8 + T RM persistence within skin, regulates epidermal CD8 + T RM dendritic extensions, and increases the frequency of IFN-γ + CD8 + T RM following local antigen challenge. Our results suggest that CD49a promotes optimal cutaneous CD8 + T RM -mediated immunity.