Abstract
This study analyzed magnetic resonance imaging (MRI) scans of Glioblastoma (GB) patients to develop an imaging-derived predictive model for assessing the extent of intratumoral CD3 T-cell infiltration. Pre-surgical T1-weighted post-contrast and T2-weighted Fluid-Attenuated-Inversion-Recovery (FLAIR) MRI scans, with corresponding mRNA expression of CD3D/E/G were obtained through The Cancer Genome Atlas (TCGA) for 79 GB patients. The tumor region was contoured and 86 image-derived features were extracted across the T1-post contrast and FLAIR images. Six imaging features—kurtosis, contrast, small zone size emphasis, low gray level zone size emphasis, high gray level zone size emphasis, small zone high gray level emphasis—were found associated with CD3 activity and used to build a predictive model for CD3 infiltration in an independent data set of 69 GB patients (using a 50-50 split for training and testing). For the training set, the image-based prediction model for CD3 infiltration achieved accuracy of 97.1% and area under the curve (AUC) of 0.993. For the test set, the model achieved accuracy of 76.5% and AUC of 0.847. This suggests a relationship between image-derived textural features and CD3 T-cell infiltration enabling the non-invasive inference of intratumoral CD3 T-cell infiltration in GB patients, with potential value for the radiological assessment of response to immune therapeutics.
Highlights
The presence and nature of the intratumoral immune response has been shown to influence tumor progression and prognosis [1], including in glioblastoma (GB), the most common primary brain tumor in humans [2,3,4]
Pre-surgical T1-weighted post-contrast and T2weighted Fluid-Attenuated-Inversion-Recovery (FLAIR) magnetic resonance imaging (MRI) scans, with corresponding mRNA expression of CD3D/E/G were obtained through The Cancer Genome Atlas (TCGA) for 79 GB patients
This suggests a relationship between image-derived textural features and CD3 T-cell infiltration enabling the noninvasive inference of intratumoral CD3 T-cell infiltration in GB patients, with potential value for the radiological assessment of response to immune therapeutics
Summary
The presence and nature of the intratumoral immune response has been shown to influence tumor progression and prognosis [1], including in glioblastoma (GB), the most common primary brain tumor in humans [2,3,4]. A variety of markers have been used for assessing an intratumoral immune response, CD3 (cluster of differentiation 3) is one such reliable marker. Robust antitumor immune responses have been shown to correlate with clinical responses to a variety of immune therapeutics [5,6,7], including tumorinfiltrating CD3 T-cells within the context of a dendritic cell therapy for GB patients [7]. Immune therapeutics are demonstrating promising response rates in GB patients despite prior notions that the central nervous system (CNS) is “immune privileged”. Determination of intratumoral immune influx and/or response to immune therapeutics currently requires either biopsy or surgery, with their inherent risks and sampling limitations
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