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Emerging targets in cancer immunotherapy

Samantha Burugu1, Amanda R Dancsok1, Torsten O Nielsen1

  • 1Department of Pathology & Laboratory Medicine, University of British Columbia Hospital, Koerner Pavilion, #G-227 2211 Wesbrook Mall, Vancouver, BC V6T 2B5, Canada.

Seminars in Cancer Biology
|October 9, 2017
PubMed

Insights

Emerging immunotherapies target novel immune checkpoints beyond CTLA-4 and PD-1/PD-L1. These new strategies aim to activate the patient

Area of Science:

  • Immunology
  • Oncology
  • Cancer Immunotherapy

Background:

  • First-generation immune checkpoint inhibitors (anti-CTLA-4, anti-PD-1/PD-L1) harness natural immune pathways for anti-tumor responses.
  • While effective in some advanced cancers, these inhibitors benefit only a subset of patients.
  • Cancers often co-opt immune homeostasis pathways to evade immune detection.

Purpose of the Study:

  • To review emerging immune targets with pre-clinical efficacy that are now in clinical trials.
  • To summarize novel co-inhibitory and co-stimulatory markers of innate and adaptive immunity.
  • To discuss combination strategies and biomarkers for cancer immunotherapy.

Main Methods:

  • Review of pre-clinical data and ongoing clinical investigations of novel immune targets.
  • Categorization of targets based on immune cell type (T lymphocytes, macrophages, NK cells).
  • Discussion of combination therapies and predictive biomarkers.

Main Results:

  • Identified T lymphocyte targets include Lymphocyte Activation Gene 3 (LAG-3), T-cell Immunoglobulin- and Mucin-domain-containing molecule 3 (TIM-3), V-domain containing Ig Suppressor of T cell Activation (VISTA), T cell ImmunoGlobulin and ITIM domain (TIGIT), B7-H3, Inducible T-cell Co-stimulator (ICOS/ICOS-L), CD27/CD70, and Glucocorticoid-Induced TNF Receptor (GITR).
  • Macrophage targets include CD47/Signal-Regulatory Protein alpha (SIRPα) and Indoleamine-2,3-Dioxygenase (IDO).
  • Natural killer cell targets include CD94/NKG2A and the Killer Immunoglobulin-like receptor (KIR) family.

Conclusions:

  • Newer immunotherapies are exploring a broader range of immune targets to enhance anti-tumor immunity.
  • These emerging targets offer potential for broader patient applicability and improved treatment outcomes.
  • Combination strategies and biomarker identification are crucial for optimizing cancer immunotherapy.
Keywords:
CheckpointsImmuno-oncologyMacrophagesNatural killerTumor-infiltrating lymphocytes

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