Next generation of immune checkpoint inhibitors and beyond

Julian A. Marin-Acevedo, Erin Marie O. Kimbrough, Yanyan Lou

Research output: Contribution to journalReview articlepeer-review

Abstract

The immune system is the core defense against cancer development and progression. Failure of the immune system to recognize and eliminate malignant cells plays an important role in the pathogenesis of cancer. Tumor cells evade immune recognition, in part, due to the immunosuppressive features of the tumor microenvironment. Immunotherapy augments the host immune system to generate an antitumor effect. Immune checkpoints are pathways with inhibitory or stimulatory features that maintain self-tolerance and assist with immune response. The most well-described checkpoints are inhibitory in nature and include the cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1 (PD-L1). Molecules that block these pathways to enhance the host immunologic activity against tumors have been developed and become standard of care in the treatment of many malignancies. Only a small percentage of patients have meaningful responses to these treatments, however. New pathways and molecules are being explored in an attempt to improve responses and application of immune checkpoint inhibition therapy. In this review, we aim to elucidate these novel immune inhibitory pathways, potential therapeutic molecules that are under development, and outline particular advantages and challenges with the use of each one of them.

Original languageEnglish (US)
Article number45
JournalJournal of Hematology and Oncology
Volume14
Issue number1
DOIs
StatePublished - Dec 2021

Keywords

  • Cancer
  • Cytotoxic T lymphocytes
  • Immune checkpoint therapy
  • Immune evasion
  • Immunotherapy
  • Immunotherapy
  • Inhibitory pathways
  • Tumor microenvironment

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Next generation of immune checkpoint inhibitors and beyond'. Together they form a unique fingerprint.

Cite this