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Biomarker Predicts Potential Benefit of Checkpoint Inhibitor Therapy for Brain Cancer Patients

By LabMedica International staff writers
Posted on 06 Dec 2021
A phosphorylated form of ERK (extracellular signal-regulated kinase) protein has been identified as a biomarker that may be used to predict which brain cancer patients might benefit from checkpoint inhibitor therapy. More...


Checkpoint inhibitor therapy (PD-1 immune checkpoint blockade) is a form of cancer treatment immunotherapy, which targets immune checkpoints, key regulators of the immune system that stimulate or inhibit its actions. Tumors can use these checkpoints to protect themselves from attacks by the immune system. Checkpoint therapy can block inhibitory checkpoints, restoring immune system function. However, most cancer patients either do not respond to immune checkpoint blockade or develop resistance to it, often because of acquired mutations that impair antigen presentation.

In this regard, only a subset of recurrent glioblastoma (rGBM) responds to anti-PD-1 immunotherapy. This cancer comprises about 30% of all brain tumors and central nervous system tumors, and 80% of all malignant brain tumors. These tumors are heavily infiltrated with immune cells of myeloid origin.

Investigators at Northwestern University (Chicago, IL, USA) examined whether activation of the MAPK/ERK signaling pathway was associated with response to PD-1 inhibition in rGBM.

Results of this study revealed that immunohistochemistry for ERK1/2 phosphorylation (p-ERK), a marker of MAPK/ERK pathway activation, was predictive of overall survival following adjuvant PD-1 blockade in two independent rGBM patient cohorts. Furthermore, single-cell RNA-sequencing and multiplex immunofluorescence analyses revealed that p-ERK was mainly localized in tumor cells. GBMs were found to contain tumor-infiltrating myeloid cells and microglia with elevated expression of MHC class II and associated genes. These findings indicated that ERK1/2 activation in rGBM was predictive of response to PD-1 blockade and was associated with a distinct myeloid cell phenotype.

“This is an important breakthrough for patients who have not had an effective treatment in the cancer drug arsenal available to them,” said senior author Dr. Adam Sonabend, associate professor of neurosurgery at Northwestern University. “It might ultimately influence the decision on how to treat glioblastoma patients and which patients should get these drugs to prolong their survival.”

The study was published in the November 29, 2021, online edition of the journal Nature Cancer.

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Northwestern University


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