Mild photothermal therapy potentiates anti-PD-L1 treatment for immunologically cold tumors via an all-in-one and all-in-control strategy

Liping Huang, Yanan Li, Yunai Du, Yiyi Zhang, Xiuxia Wang, Yuan Ding, Xiangliang Yang, Fanling Meng, Jiasheng Tu (), Liang Luo () and Chunmeng Sun ()
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Liping Huang: Huazhong University of Science and Technology
Yanan Li: China Pharmaceutical University
Yunai Du: China Pharmaceutical University
Yiyi Zhang: Huazhong University of Science and Technology
Xiuxia Wang: Huazhong University of Science and Technology
Yuan Ding: China Pharmaceutical University
Xiangliang Yang: Huazhong University of Science and Technology
Fanling Meng: Huazhong University of Science and Technology
Jiasheng Tu: China Pharmaceutical University
Liang Luo: Huazhong University of Science and Technology
Chunmeng Sun: China Pharmaceutical University

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract One of the main challenges for immune checkpoint blockade antibodies lies in malignancies with limited T-cell responses or immunologically “cold” tumors. Inspired by the capability of fever-like heat in inducing an immune-favorable tumor microenvironment, mild photothermal therapy (PTT) is proposed to sensitize tumors to immune checkpoint inhibition and turn “cold” tumors “hot.” Here we present a combined all-in-one and all-in-control strategy to realize a local symbiotic mild photothermal-assisted immunotherapy (SMPAI). We load both a near-infrared (NIR) photothermal agent IR820 and a programmed death-ligand 1 antibody (aPD-L1) into a lipid gel depot with a favorable property of thermally reversible gel-to-sol phase transition. Manually controlled NIR irradiation regulates the release of aPD-L1 and, more importantly, increases the recruitment of tumor-infiltrating lymphocytes and boosts T-cell activity against tumors. In vivo antitumor studies on 4T1 and B16F10 models demonstrate that SMPAI is an effective and promising strategy for treating “cold” tumors.

Date: 2019
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DOI: 10.1038/s41467-019-12771-9

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