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

Nat Commun. 2019 Oct 25;10(1):4871. doi: 10.1038/s41467-019-12771-9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Immunological / pharmacology*
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / 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
  • Indocyanine Green / pharmacology
  • Lipids
  • Lymphocytes, Tumor-Infiltrating / drug effects
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Melanoma, Experimental / immunology*
  • Mice
  • NIH 3T3 Cells
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • Tumor Microenvironment / immunology

Substances

  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen
  • Delayed-Action Preparations
  • Gels
  • IR 820
  • Lipids
  • Indocyanine Green