Synergies of Targeting Tumor Angiogenesis and Immune Checkpoints in Non-Small Cell Lung Cancer and Renal Cell Cancer: From Basic Concepts to Clinical Reality

Int J Mol Sci. 2017 Oct 31;18(11):2291. doi: 10.3390/ijms18112291.


In recent years, considerable advances concerning therapeutic strategies in patients with metastatic cancer have been achieved. Particularly in renal cell cancer (RCC) and advanced stage non-small cell lung cancer (NSCLC), immune-activating and antiangiogenic (AA) drugs (i.e., checkpoint antibodies and vascular endothelial growth factor (VEGF)/VEGF receptors (VEGFR) targeting compounds, respectively) have been successfully developed. As immune-effector cells have to enter the tumor, it is tempting to speculate that the combination of immunotherapy with AA treatment may induce synergistic effects. In this short review, we explore the theoretical background and the therapeutic potential of this novel treatment option for patients with advanced RCC or NSCLC. We discuss the growing body of evidence that pro-angiogenic factors negatively modulate the T-cell-mediated immune response and examine the preclinical evidence for testing combined immune-activating and AA therapy concepts in clinical practice. Particular attention will also be paid to potential novel treatment-related adverse events induced by combination treatment.

Keywords: VEGF inhibition; angiogenesis; checkpoint inhibition; immunotherapy; non-small cell lung cancer; renal cell cancer.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Carcinoma, Renal Cell / therapy*
  • Humans
  • Immunotherapy / methods*
  • Kidney Neoplasms / therapy*
  • Lung Neoplasms / therapy*


  • Angiogenesis Inhibitors
  • Antineoplastic Agents, Immunological