Immune checkpoint blockade therapy has become a first-line treatment in various cancers.But there are only a small percent of colorectal patients responding to PD-1/PD-L1 blockage immunotherapy.How to increase their treatment efficacy is an urgent and clinically unmet need.It is acknowledged that immunogenic cell death (ICD) induced by some specific chemotherapy can enhance antitumor immunity.Chemo-based combination therapy can yield improved outcomes by activating the immune system to eliminate the tumor,compared with monotherapy.Here,we develop a PD-L1-targeting immune liposome (P-Lipo) for co-delivering irinotecan (IRI) and JQ1,and this system can successfully elicit antitumor immunity in colorectal cancer through inducing ICD by IRI and interfering in the immunosuppressive PD-1/PD-L1 pathway by JQ1.P-Lipo increases intratumoral drug accumulation and promotes DC maturation,and thereby facilitates adaptive immune responses against tumor growth.The remodeling tumor immune microenvironment was reflected by the increased amount of CD8+ T cells and the release of IFN-γ,and the reduced CD4+Foxp3+ regulatory T cells (Tregs).Collectively,the P-Lipo codelivery system provides a chemo-immunotherapy strategy that can effectively remodel the tumor immune microenvironment and activate the host immune system and arrest tumor growth.