AUTHOR=Xiao Guixiu , Zhao Yujie , Wang Xueyan , Zeng Chuan , Luo Feng , Jing Jing 

TITLE=Photothermally sensitive gold nanocage augments the antitumor efficiency of immune checkpoint blockade in immune “cold” tumors

JOURNAL=Frontiers in Immunology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1279221

DOI=10.3389/fimmu.2023.1279221

ISSN=1664-3224

ABSTRACT=Immune checkpoint blockade (ICB) has transformed the therapeutic landscape of multiple malignant tumors. However, the clinical benefits from this regimen remain limited, especially in immune “cold” tumors that lack infiltrated T cells. To address this problem, we developed a second near-infrared (NIR-II) light-activated nanosystem AuNC@SiO2@HA to mediate photothermal therapy (PTT) and synergize with anti-PD-1 blockade. The AuNC@SiO2@HA nanosystem consists of a gold nanocage (AuNC) kernel with absorption at 1064 nm, a silica shell, and a functionalized hyaluronic acid (HA) polymer. Tumor cells can efficiently take up the nanocomposites, which transform the optical energy into heat energy upon 1064 nm laser irradiation and subsequently result in tumor cell apoptosis in vitro. In a mouse melanoma model with a “cold” immune microenvironment, the nanocomposites can efficiently accumulate in the tumor region after intravenous injection and elevate the temperature of the tumor region after NIR-II laser irradiation. The mechanism study proved that AuNC@SiO2@HA mediated PTT effectively induced immunogenic cell death (ICD), released tumor-specific neoantigens, and promoted the infiltration of cytotoxic lymphocytes in vivo. When combined with anti-PD-1 antibodies, this therapy can stimulate robust T lymphocyte immune responses and significantly inhibit tumor growth. More importantly, the combination of AuNC@SiO2@HA mediated PTT and anti-PD-1 immunotherapy could convert immune “cold” tumors into “hot” ones, which could benefit patients without sufficient antigen-specific T cells. In conclusion, this study provided a novel strategy for the treatment of immune “cold” tumors by combining the gold cage nanosystem-mediated PTT with anti-PD-1 immunotherapy.