A combination of protein phosphatase 2A inhibition and checkpoint immunotherapy: a perfect storm

Autor: Mary C. Clark, Rongze Olivia Lu, Winson S. Ho, Matheus Henrique Dias, René Bernards, Stephen J. Forman
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Molecular Oncology, Vol 18, Iss 10, Pp 2333-2337 (2024)
Druh dokumentu: article
ISSN: 1878-0261
1574-7891
DOI: 10.1002/1878-0261.13687
Popis: Immune checkpoint blockade has emerged as a potent new tool in the war on cancer. However, only a subset of cancer patients benefit from this therapeutic modality, sparking a search for combination therapies to increase the fraction of responding patients. We argue here that inhibition of protein phosphatase 2A (PP2A) is a promising approach to increase responses to immune checkpoint blockade and other therapies that rely on the presence of tumor‐reactive T cells. Inhibition of PP2A increases neoantigen expression on tumor cells, activates the cGAS/STING pathway, suppresses regulatory T cells, and increases cytotoxic T cell activation. In preclinical models, inhibition of PP2A synergizes with immune checkpoint blockade and emerging evidence indicates that patients who have tumors with mutations in PP2A respond better to immune checkpoint blockade. Therefore, inhibition of PP2A activity may be an effective way to sensitize cancer cells to immune checkpoint blockade and cell‐based therapies using tumor‐reactive T cells.
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