Related Experiment Video

Updated: Feb 9, 2026

Author Spotlight: Magnetic Fluorescent Bead-Based Dual-Reporter Flow Analysis of PDL1-Vaxx Peptide Vaccine-Induced Antibody Blockade of the PD-1/PD-L1 Interaction
10:18

Author Spotlight: Magnetic Fluorescent Bead-Based Dual-Reporter Flow Analysis of PDL1-Vaxx Peptide Vaccine-Induced Antibody Blockade of the PD-1/PD-L1 Interaction

Published on: July 7, 2023

1.7K

Pharmacologic inhibition of protein phosphatase-2A achieves durable immune-mediated antitumor activity when combined

Winson S Ho1, Herui Wang2, Dominic Maggio1

  • 1Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, 20892, USA.

Nature Communications
|May 31, 2018
PubMed

Insights

Inhibiting protein phosphatase-2A (PP2A) with LB-100 synergizes with anti-PD-1 therapy to boost anticancer immunity. This combination therapy leads to durable, T-cell dependent tumor regression and establishes protective memory.

Area of Science:

  • Immunology
  • Oncology
  • Pharmacology

Background:

  • Protein phosphatase-2A (PP2A) inhibition shows potential for enhancing anticancer immunity.
  • Currently, no drugs specifically target PP2A for therapeutic use.

Purpose of the Study:

  • To investigate the synergistic effect of a PP2A inhibitor, LB-100, combined with anti-PD-1 (aPD-1) blockade in preclinical cancer models.
  • To elucidate the mechanisms underlying the observed antitumor immune response.

Main Methods:

  • Utilized murine CT26 colon cancer and B16 melanoma models.
  • Administered LB-100 in combination with aPD-1 blockade.
  • Analyzed tumor-infiltrating lymphocytes, T-cell populations (effector and regulatory), cytokine profiles, and mTORC1 signaling.

Main Results:

  • Combination therapy resulted in synergistic, durable, immune-mediated antitumor responses and tumor regression.
  • The effect was T-cell dependent, with enhanced effector T-cell and reduced regulatory T-cell infiltration in tumors.
  • LB-100 activated mTORC1 signaling, decreased naive CD4+ T-cell differentiation into regulatory T cells, and shifted cytokine profiles towards Th1.
  • Tumor clearance led to antigen-specific secondary protective immunity.

Conclusions:

  • PP2A inhibition, exemplified by LB-100, combined with aPD-1 blockade offers a promising synergistic strategy for cancer immunotherapy.
  • This combination enhances T-cell mediated antitumor immunity and establishes long-term protection.
  • The findings underscore the translational potential of combining PP2A inhibitors with immune checkpoint inhibitors.

More Related Videos

Recombinant α- β- and γ-Synucleins Stimulate Protein Phosphatase 2A Catalytic Subunit Activity in Cell Free Assays09:36

Recombinant α- β- and γ-Synucleins Stimulate Protein Phosphatase 2A Catalytic Subunit Activity in Cell Free Assays

Published on: August 13, 2017

7.1K
Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology07:04

Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology

Published on: May 2, 2025

1.2K

Related Concept Videos

Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
15.2K
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

4.5K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
6.0K
Cell-mediated Immune Responses01:40

Cell-mediated Immune Responses

Overview
84.2K
Neuromuscular Junction And Blockade01:29

Neuromuscular Junction And Blockade

The site of chemical communication between a motor neuron and a muscle fiber is called the neuromuscular junction (NMJ). The end of the motor neuron at the NMJ divides into a cluster of synaptic end bulbs. The cytoplasm of these bulbs consists of synaptic vesicles enclosing acetylcholine molecules, the principal neurotransmitter released at the NMJ. The region opposite the synaptic bulb that ends in the muscle fiber is called the motor end plate, which has acetylcholine receptors. Within the...
5.1K
Active versus Passive Immunity01:31

Active versus Passive Immunity

Immunity, along with the ability to limit pathogen growth to prevent significant body tissue damage, can be gained either by (1) actively developing an immune response within the individual after exposure to a pathogen or after getting vaccinated or (2) passively transferring immune components from an immune individual to one who is nonimmune. Both these forms of immunity can be found naturally and in medical practices.
Active Immunity
Active immunity refers to the resistance one develops...
10.9K