Enhanced systemic antitumor efficacy of PD-1/PD-L1 blockade with immunological response induced by photodynamic therapy

Thorac Cancer. 2024 Jun;15(18):1429-1436. doi: 10.1111/1759-7714.15325. Epub 2024 May 13.

Abstract

Background: Photodynamic therapy (PDT) is an antitumor therapy and has traditionally been regarded as a localized therapy in itself. However, recent reports have shown that it not only exerts a direct cytotoxic effect on cancer cells but also enhances body's tumor immunity. We hypothesized that the immunological response induced by PDT could potentially enhance the efficacy of programmed death-1 (PD-1) / programmed death-ligand 1 (PD-L1) blockade.

Methods: The cytotoxic effects of PDT on colon 26 cells were investigated in vitro using the WST assay. We investigated whether the antitumor effect of anti-PD-1 antibodies could be amplified by the addition of PDT. We performed combination therapy by randomly allocating tumor-bearing mice to four treatment groups: control, anti-PD-1 antibodies, PDT, and a combination of anti-PD-1 antibodies and PDT. To analyze the tumor microenvironment after treatment, the tumors were resected and pathologically evaluated.

Results: The viability rate of colon 26 cells decreased proportionally with the laser dose. In vivo experiments for combined PDT and anti-PD-1 antibody treatment, combination therapy showed an enhanced antitumor effect compared with the control. Immunohistochemical findings of the tumor microenvironment 10 days after PDT indicated that the number of CD8+ cells, the area of Iba-1+ cells and the area expressing PD-L1 were significantly higher in tumors treated with combination therapy than in tumors treated with anti-PD-1 antibody alone, PDT alone, or the control.

Conclusions: PDT increased immune cell infiltration into the tumor microenvironment. The immunological response induced by PDT may enhance the efficacy of PD-1/PD-L1 blockade.

Keywords: anti‐PD‐1; combination therapy; immunological response; photodynamic therapy.

MeSH terms

  • Animals
  • B7-H1 Antigen* / antagonists & inhibitors
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / immunology
  • Colonic Neoplasms / pathology
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology
  • Immune Checkpoint Inhibitors / therapeutic use
  • Mice
  • Photochemotherapy* / methods
  • Programmed Cell Death 1 Receptor* / antagonists & inhibitors
  • Tumor Microenvironment / drug effects

Substances

  • B7-H1 Antigen
  • Programmed Cell Death 1 Receptor
  • Immune Checkpoint Inhibitors
  • CD274 protein, human