Immune checkpoint inhibitor treatment of brain metastasis associated with a less invasive growth pattern, higher T-cell infiltration and raised tumor ADC on diffusion weighted MRI

Zakaria, Rasheed ORCID: 0000-0001-6826-2662, Jenkinson, Michael D ORCID: 0000-0003-4587-2139, Radon, Mark, Das, Kumar, Poptani, Harish ORCID: 0000-0002-0593-3235, Rathi, Nitika and Rudland, Philip S ORCID: 0000-0002-7491-0846 (2023) Immune checkpoint inhibitor treatment of brain metastasis associated with a less invasive growth pattern, higher T-cell infiltration and raised tumor ADC on diffusion weighted MRI. CANCER IMMUNOLOGY IMMUNOTHERAPY, 72 (10). pp. 3387-3393.

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Official URL: http://dx.doi.org/10.1007/s00262-023-03499-z

Abstract

<h4>Background</h4>Brain metastases are the most common intracranial tumors with an increasing incidence. They are an important cause of morbidity and mortality in patients with solid organ cancer and a focus of recent clinical research and experimental interest. Immune checkpoint inhibitors are being increasingly used to treat solid organ cancers.<h4>Methods</h4>To determine whether immune checkpoint inhibitors were biologically effective in the brain, we compared melanoma brain metastasis samples where treatment with ipilimumab had occurred preoperatively to those who had not received any immune modulating therapy and looked for histopathological (invasion, vascularity, metastasis inducing proteins, matrix metalloproteinases, immune cell infiltration, tissue architecture) and advanced MRI differences (diffusion weighted imaging).<h4>Results</h4>Co-localized tissue samples from the same regions as MRI regions of interest showed significantly lower vascularity (density of CD34 + vessels) in the core and higher T-cell infiltration (CD3 + cells) in the leading edge for ipilimumab-treated brain metastasis samples than for untreated cases and this correlated with a higher tumor ADC signal at post-treatment/preoperative MRI brain.<h4>Conclusions</h4>Treatment of a melanoma brain metastasis with ipilimumab appears to cause measurable biological changes in the tumor that can be correlated with post-treatment diffusion weighted MRI imaging, suggesting both a mechanism of action and a possible surrogate marker of efficacy.

Item Type:	Article
Uncontrolled Keywords:	Brain metastasis, Immunotherapy, Malignant melanoma, MRI, DWI, ADC
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	24 Jul 2023 14:53
Last Modified:	09 Sep 2023 01:20
DOI:	10.1007/s00262-023-03499-z
Open Access URL:	https://link.springer.com/article/10.1007/s00262-0...
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3171844