Combined application of bevacizumab and PD-1 blockade displays durable treatment effects by increasing the infiltration and cytotoxic function of CD8+ T cells in lung cancer

Immunotherapy. 2022 Jun;14(9):695-708. doi: 10.2217/imt-2021-0196. Epub 2022 May 16.

Abstract

Aim: VEGF/VEGFR inhibitors may help immune checkpoint inhibitors expand the population that will benefit from treatment. The authors investigated the efficacy of combined bevacizumab and PD-1 antibody. Materials & methods: C57BL/6J mice were injected subcutaneously with 1 × 106 Lewis lung carcinoma cells. The mice were intraperitoneally injected with 0.25 mg anti-PD-1 inhibitors and/or 15 mg/kg bevacizumab. Tumor tissues were harvested. The authors reported that a non-small cell lung cancer patient received 200 mg PD-1 antibody combined with 7.5 mg/kg bevacizumab as fourth-line treatment. Results: Bevacizumab combined with PD-1 antibody induced a strong and durable antitumor effect. Bevacizumab combined with PD-1 antibody improved abnormal tumor vessels and enhanced the cytotoxic function and infiltration of T lymphocytes. The patient's survival time was significantly prolonged. Conclusion: Bevacizumab combined with anti-PD-1 antibody induces a durable antitumor effect by increasing the infiltration and cytotoxic function of CD8+ T cells in lung cancer.

Keywords: CD8+ T cells; NSCLC; VEGF; anti-PD-1 antibody; bevacizumab; tumor microenvironment; tumor vessels.

Plain language summary

Immune checkpoint inhibitors can improve long-term survival in advanced non-small-cell lung cancer, but the promising clinical benefit was only observed in a minority of patients. The combination of VEGF/VEGFR inhibitors and immune checkpoint inhibitors has become an attractive strategy. In this study, lung carcinoma mouse models were used to investigate the therapeutic efficacy of combined bevacizumab and anti-PD-1 antibody. The authors demonstrated that the combined application of bevacizumab and PD-1 blockade displays durable treatment effects by increasing the infiltration and cytotoxic function of CD8+ T cells. This study also reports a non-small-cell lung cancer patient who benefited from this treatment regimen as fourth-line therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bevacizumab / therapeutic use
  • CD8-Positive T-Lymphocytes
  • Carcinoma, Non-Small-Cell Lung*
  • Cell Line, Tumor
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Lung Neoplasms* / pathology
  • Mice
  • Mice, Inbred C57BL
  • Programmed Cell Death 1 Receptor
  • Tumor Microenvironment

Substances

  • Immune Checkpoint Inhibitors
  • Programmed Cell Death 1 Receptor
  • Bevacizumab