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Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes
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Glycogen synthase 3 (GSK-3) regulation of PD-1 expression and and its therapeutic implications

Janna Krueger1, Christopher E Rudd1, Alison Taylor2

  • 1Division of Immunology-Oncology, Research Center Maisonneuve-Rosemont Hospital, Montreal, Quebec H1T 2M4, Canada; Département de Medicine, Université de Montréal, Montreal, Quebec H3C 3J7, Canada.

Seminars in Immunology
|October 13, 2019
PubMed

Insights

Immune checkpoint blockade (ICB) shows promise in cancer treatment, but limitations exist. Inhibiting glycogen synthase kinase 3 (GSK-3) down-regulates PD-1, offering a new strategy for cancer immunotherapy.

Area of Science:

  • Oncology
  • Immunology
  • Pharmacology

Background:

  • Immune checkpoint blockade (ICB) therapies targeting CTLA-4 and PD-1/PD-L1 have advanced cancer treatment.
  • Combinations of antibodies against CTLA-4, PD-1, TIM3, TIGIT, and LAG3 are being explored.
  • Limitations of current ICB include cost, tumor penetration, receptor accessibility, and inflammatory side effects.

Purpose of the Study:

  • To review the potential of small molecule inhibitors (SMIs) targeting intracellular pathways for cancer immunotherapy.
  • To highlight the role of glycogen synthase kinase 3 (GSK-3) inhibition in down-regulating PD-1 expression.

Main Methods:

  • Review of existing literature on ICB and GSK-3 inhibition.
  • Analysis of preclinical and clinical data on SMIs in cancer immunotherapy.

Main Results:

  • GSK-3 inhibition was shown to down-regulate PD-1 expression in infectious diseases and cancer.
  • SMIs offer an alternative approach to antibody-based ICB.

Conclusions:

  • Targeting intracellular pathways with SMIs presents a promising strategy to overcome limitations of current ICB therapies.
  • GSK-3 inhibitors represent a potential therapeutic avenue for enhancing cancer immunotherapy.
Keywords:
AtezolizumabAvelumabCancer immunotherapyCemiplimabDurmalumabGSK-3Immune checkpointNivolumabPD-1PD-L1PembrolizumabSMI

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