Reversing Immunosuppression in Hypoxic and Immune‐Cold Tumors with Ultrathin Oxygen Self‐Supplementing Polymer Nanosheets under Near Infrared Light Irradiation

Abstract

Solid tumors are characterized by a hypoxic and immunologically “cold” microenvironment that dramatically limits the therapeutic outcomes of immunotherapy. Thus, strategies and materials that are capable of reversing immunosuppression in immune‐cold tumors are highly desired. Herein, it is reported that oxygen (O2) self‐supplementing conjugated microporous polymer nanosheets can be utilized to elicit a robust antitumor T cell immune response in the hypoxic and immunosuppressive tumor microenvironment. The ultrathin nanosheets can generate O2 through the water splitting reaction and produce massive reactive oxygen species (ROS) under near infrared light irradiation. Meanwhile, the unique photothermal property of the conjugated polymer nanosheets generates hyperthermia under irradiation. Consequently, they are able to maximize the immunogenic cell death (ICD) performance by inducing adequate damage‐related molecular patterns in hypoxic tumors. Other than fostering T cell infiltration by the elicited ICD, the loaded indoleamine 2,3‐dioxygenase in nanosheets can reverse the immunosuppression and empower ICD effect for efficient T cells priming. In vivo experiments conclusively prove that the designed polymer nanosheets exhibit great potential for tumor eradication, metastasis prevention, as well as long‐term survival. Such a photocatalytic platform opens up new paths for reversing immunosuppression in immune‐cold tumors and broadens the application of polymer‐based nanosheets for cancer therapy.

Nitric Oxide Induces Immunogenic Cell Death and Potentiates Cancer Immunotherapy

“…We further investigated whether the released DAMPs could stimulate the activation of DCs . Dying 4T1 cells were obtained after incubation with GSNO or SNP for 12 h. Murine bone-marrow-derived dendritic cells (BMDCs) were then cocultured with the dying 4T1 cells (Figure S18a).…”

Nanotechnology for Boosting Cancer Immunotherapy and Remodeling Tumor Microenvironment: The Horizons in Cancer Treatment

“…Similarly, Jiang et al utilized ultrathin oxygen self-supplementing polymer nanosheets to generate O 2 through the water splitting reaction for alleviating tumor hypoxia and produce massive ROS for ICD boosting. Experiments conclusively proved that the nanosheets coordinated IDO inhibitor could reverse the immunosuppression and foster T cell immune response in hypoxic and immune-cold tumors …”

Nanomedicines Targeting Metabolism in the Tumor Microenvironment

“…The kynurenine pathway is controlled by the rate-limiting enzyme indoleamine-2,3-dioxygenase (IDO1) (Platten et al, 2019). IDO1-modulation nanoparticles are always used as an immunometabolism drug to block kynurenine metabolic pathways (Jiang et al, 2021;Liu et al, 2021;Wang et al, 2022b). A work utilizes aza-fused conjugated microporous polymer (aCMP) nanosheets inducing dual-type of ICD and the interference of the IDO pathway in hypoxic tumors (Jiang et al, 2021).…”

“…IDO1-modulation nanoparticles are always used as an immunometabolism drug to block kynurenine metabolic pathways (Jiang et al, 2021;Liu et al, 2021;Wang et al, 2022b). A work utilizes aza-fused conjugated microporous polymer (aCMP) nanosheets inducing dual-type of ICD and the interference of the IDO pathway in hypoxic tumors (Jiang et al, 2021). Furthermore, cancer cells secret PGE2, thereby directly inactivating T cells.…”