Hyperbaric Oxygen Boosts PD‐1 Antibody Delivery and T Cell Infiltration for Augmented Immune Responses Against Solid Tumors

Abstract

Aberrant mechanical properties and immunosuppression are the two key factors that limit the antitumor efficacy of T cell immune checkpoint blockade inhibitors, e.g., programmed cell death‐1 antibody (PD‐1 Ab), against solid tumors in the clinic. This study leverages hyperbaric oxygen (HBO) for the first time to address these two issues and reports the PD‐1‐Ab‐mediated immune responses against various stroma‐rich solid malignancies. The results demonstrate that HBO promoted PD‐1 Ab delivery and T cells infiltration into tumor parenchyma by depleting the extracellular matrix's main components, such as collagen and fibronectin. Furthermore, HBO disrupts hypoxia‐mediated immunosuppression and helps PD‐1 Ab trigger robust cytotoxic T lymphocytes and long‐lasting immunological memory to inhibit tumor relapses. Such enhanced immune responses are effective in solid tumors from rodents and the cancer cells from hepatocellular carcinoma patients. The results illustrate that HBO bolsters antitumor efficacy of PD‐1 Ab, and the HBO–PD‐1 Ab combination is a promising stroma‐rich solid tumors’ treatment in the clinic.

Enhanced Therapeutic Efficacy of Combining Losartan and Chemo-Immunotherapy for Triple Negative Breast Cancer

“…Furthermore, dense stroma and resulting hypoxia are associated with the immune-suppressive tumor microenvironment ( 26 , 39 ), with polarization of M2 TAMs and insufficient accumulation of cytotoxic immune cells. Several studies pointed out that strategy focusing on modulation ECM and hypoxia status might yield promising results in enhancing anti-tumor immunity ( 16 , 22 , 40 ). The depleting ECM resulted in relieving tumor hypoxia, as verified by immunofluorescence imaging.…”

Hyperbaric oxygen facilitates teniposide-induced cGAS-STING activation to enhance the antitumor efficacy of PD-1 antibody in HCC

“…17 As a conventional therapy, HBO has attracted much attention in cancer treatment in recent years. [18][19][20] Here, to maximize cGAS-STING activation in HCC, we combined two therapies approved by the Food and Drug Administration (FDA): teniposide and HBO. By implementing teniposide chemotherapy, we achieved stronger STING activation than routine HCC chemotherapy drugs.…”

“…18 Furthermore, HBO also promoted immune responses against solid tumors by enhancing PD-1 Ab delivery and subsequent T cell infiltration. 19 Based on the excellent tissue oxygenation capability of HBO, we wondered whether teniposide-induced cGAS-STING activation could be promoted after HBO administration. By reoxygenating hypoxic tumor cells in vitro, we observed the rapid rescue of cGAS expression and reactivation of teniposide-induced cGAS-STING signaling, Open access which provided a therapeutic basis for HBO application.…”

Autocatalytic oncotherapy nanosystem with glucose depletion for the cascade amplification of hypoxia-activated chemotherapy and H2O2-dependent chemodynamic therapy

“…1 It has been found that hypoxia is a major factor that largely results in resistance of tumor to chemotherapy, 2,3 radiotherapy, 4,5 photodynamic therapy (PDT), 6,7 sonodynamic therapy (SDT) 8 and so on, greatly reducing the therapeutic efficiency of many tumor treatments. 9 To solve this problem, various strategies have been employed to counter tumor hypoxia in recent years, including breathing hyperbaric oxygen, [10][11][12][13][14] tumor targeted oxygen delivery by perfluorocarbon-/hemoglobin-based systems [15][16][17] or microbubbles, 18,19 and in situ oxygen generation based on intracellular H 2 O 2 decomposition catalyzed by nanoenzymes like quantum dots, 20,21 metal-based nanoparticles 22,23 or catalase. 24 Despite being promising, some potential defects limit the utility of these strategies, such as hyperoxic seizures and barotrauma, poor oxygen loading rates, rapid oxygen leakage and low intratumoral H 2 O 2 concentration.…”