Nanoscale Reduced Graphene Oxide-Mediated Photothermal Therapy Together with IDO Inhibition and PD-L1 Blockade Synergistically Promote Antitumor Immunity

Mengmeng Yan, Yijia Liu, Xianghui Zhu, Xiaoli Wang, Lanxia Liu, Hongfan Sun, Chun Wang, Deling Kong, Guilei Ma

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Despite the potential efficacy of immune checkpoint blockade for effective treatment of cancer, this therapeutic modality is not generally curative, and only a fraction of patients respond. Combination approaches provide strategies to target multiple antitumor immune pathways to induce synergistic antitumor immunity. Here, a multi-combination immunotherapy, including photothermal therapy (PTT), indoleamine-2,3-dioxygenase (IDO) inhibition, and programmed cell death-ligand 1 (PD-L1) blockade, is introduced for inducing synergistic antitumor immunity. We designed a multifunctional IDO inhibitor (IDOi)-loaded reduced graphene oxide (rGO)-based nanosheets (IDOi/rGO nanosheets) with the properties to directly kill tumor cells under laser irradiation and in situ trigger antitumor immune response. In vivo experiments further revealed that the triggered immune response can be synergistically promoted by IDO inhibition and PD-L1 blockade; the responses included the enhancement of tumor-infiltrating lymphocytes, including CD45 + leukocytes, CD4 + T cells, CD8 + T cells, and NK cells; the inhibition of the immune suppression activity of regulator T cells (T regs ); and the production of INF-γ. We also demonstrate that the three combinations of PTT, IDO inhibition, and PD-L1 blockade can effectively inhibit the growth of both irradiated tumors and tumors in distant sites without PTT treatment. This work can be thought of as an important proof of concept to target multiple antitumor immune pathways to induce synergistic antitumor immunity.

Original languageEnglish (US)
Pages (from-to)1876-1885
Number of pages10
JournalACS Applied Materials and Interfaces
Volume11
Issue number2
DOIs
StatePublished - Jan 16 2019
Externally publishedYes

Keywords

  • IDO inhibition
  • PD-L1
  • combinatorial immunotherapy
  • photothermal therapy
  • reduced graphene oxide

PubMed: MeSH publication types

  • Journal Article

Fingerprint Dive into the research topics of 'Nanoscale Reduced Graphene Oxide-Mediated Photothermal Therapy Together with IDO Inhibition and PD-L1 Blockade Synergistically Promote Antitumor Immunity'. Together they form a unique fingerprint.

  • Cite this