Challenges and advances for the treatment of renal cancer patients with brain metastases: From immunological background to upcoming clinical evidence on immune-checkpoint inhibitors

Crit Rev Oncol Hematol. 2021 Jul:163:103390. doi: 10.1016/j.critrevonc.2021.103390. Epub 2021 Jun 4.

Abstract

The introduction of checkpoint inhibitors (ICIs) in renal cell carcinoma (RCC) treatment landscape, resulted in improvements in overall survival (OS) in metastatic patients. Brain metastases (BMs) are a specific metastatic site of interest representing a predictive factor of poor prognosis. Patients with BMs were usually excluded from prospective clinical trials in the past. Despite recent evidence suggest the efficacy and safety of ICIs, the BMs treatment remains a challenge; the immunotherapy responsiveness seems to be multifactorial and dependent on several factors, such as the genetic intratumor heterogeneity and the immunosuppressive role of the brain tumor microenvironment. This review, starting from the immunological background in RCC BMs, provide an overview of the upcoming evidence from clinical trials, address the issues related to the neuroradiological immunotherapy response evaluation and, with a look to the future, describes how the epigenetic modulation of immune evasion could represent a background for new therapeutic strategies.

Keywords: Brain metastases; Brain tumor microenvironment; Epigenetic remodeling; Immune-checkpoint inhibitors; Immunotherapy; Neuroradiological response evaluation; Renal cancer; Renal cell carcinoma.

Publication types

  • Review

MeSH terms

  • Brain Neoplasms* / drug therapy
  • Carcinoma, Renal Cell* / drug therapy
  • Humans
  • Immune Checkpoint Inhibitors
  • Kidney Neoplasms* / drug therapy
  • Prospective Studies
  • Tumor Microenvironment

Substances

  • Immune Checkpoint Inhibitors