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

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.
Authors	Liping Huang, Yanan Li, Yunai Du, Yiyi Zhang, Xiuxia Wang, Yuan Ding, Xiangliang Yang, Fanling Meng, Jiasheng Tu, Liang Luo, Chunmeng Sun
Journal	Nature communications (Nat Commun) Vol. 10 Issue 1 Pg. 4871 (10 25 2019) ISSN: 2041-1723 [Electronic] England
PMID	31653838 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antineoplastic Agents, Immunological B7-H1 Antigen Delayed-Action Preparations Gels IR 820 Lipids Indocyanine Green
Topics	Animals Antineoplastic Agents, Immunological (pharmacology) B-Lymphocytes (drug effects, immunology) B7-H1 Antigen (antagonists & inhibitors) Cell Line, Tumor Combined Modality Therapy Delayed-Action Preparations Gels Humans Hyperthermia, Induced (methods) Immunotherapy Indocyanine Green (analogs & derivatives, pharmacology) Lipids Lymphocytes, Tumor-Infiltrating (drug effects, immunology) Melanoma, Experimental (immunology) Mice NIH 3T3 Cells T-Lymphocytes (drug effects, immunology) Tumor Microenvironment (immunology)

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