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MRI histogram analysis of tumor-infiltrating CD8+ T cell levels in patients with glioblastoma
Caiqiang Xue1, Qing Zhou1, and Junlin Zhou1
1Lanzhou University Second Hospital, Lanzhou, China

Synopsis

Keywords: Tumors, Tumor

CD8+ T cell infiltration in tumors is a powerful predictor of the clinical and postoperative prognosis of GBM patients. Immunohistochemical staining was used to assess tumor-infiltrating CD8+ T cell expression in patient-derived tumor tissue samples. Histogram analysis of GBM was performed using Firevoxel software. Among the T1C histogram features, the CV, mean, 5th, 10th, 25th, and 50th percentiles were correlated with the levels of CD8+ T cells. The ROC curve analysis revealed that the CV had the highest AUC value (0.783). Histogram analysis is an efficient non-invasive imaging modality for the prediction of tumor-infiltrating CD8+ T cells in glioblastoma.

Introduction

Glioblastoma (GBM) is the most common malignant brain tumor and has a median overall survival (OS) of 12–18 months. CD8+ lymphocytes limit tumor cell growth, inhibit tumor infiltration, and mediate tumor elimination. Therefore, CD8+ T cell infiltration in tumors is a powerful predictor of the clinical and postoperative prognosis of GBM patients. Therefore, preoperative assessment of tumor-infiltrating CD8+ T cells is necessary for informing the treatment strategies and prognosis of patients with GBM. Histogram analysis is a post-processing technique for measuring several parameters and it can better elucidate the tissue microstructure . We aimed to investigate the predictive utility of preoperative T1C histograms for the levels of tumor-infiltrating CD8+ T cells in patients with GBM.

Methods

This retrospective study was approved by the local institutional review board, which waived the requirement for informed consent. We retrospectively analyzed the pathological and imaging data of 61 patients with GBM confirmed by surgery and pathology. Moreover, the levels of tumor-infiltrating CD8+ T cells in tumor tissue samples obtained from the patients were quantified through immunohistochemical staining and evaluated with respect to overall survival. The patients were divided into the high and low CD8 expression groups. Preoperative T1-weighted contrast-enhanced (T1C) histogram parameters of patients with GBM were extracted using Firevoxel software. We investigated the correlation between the histogram feature parameters and CD8+ T cells. We performed statistical analyses of the T1C histogram parameters in both groups and identified characteristic parameters with significant between-group differences. Additionally, we performed a receiver operating characteristic curve (ROC) analysis to determine the predictive utility of these parameters.

Results

The levels of tumor-infiltrating CD8+ T cells were positively associated with overall survival in patients with GBM (P = 0.0156). Among the T1C histogram features, the mean, 5th, 10th, 25th, and 50th percentiles were negatively correlated with the levels of CD8+ T cells. Moreover, the coefficient of variation (CV) was positively correlated with the levels of CD8+ T cells (all P < 0.05). There was a significant between-group difference in the CV, 1st, 5th, 10th, 25th, and 50th percentiles (all p < 0.05). The ROC curve analysis revealed that the CV had the highest AUC value (0.783; 95% confidence interval: 0.658–0.878), with sensitivity and specificity values of 0.784 and 0.750, respectively, for distinguishing between the groups.

Discussion

Percentile is the most widely used parameter in histogram analysis. In our study, there was a significant between-group difference in the 1st, 5th, 10th, 25th, and 50th percentiles; however, there was no significant between-group difference in the mean values. This indicates that the percentile can better reflect the internal lesion characteristics. The CV describes the degree of dispersion of the means of the characteristic values of the lesions. A larger CV indicates more deviation of the data from the mean value, and thus greater variability of the lesions. In our study, the CV values were significantly higher in the high CD8 expression group than in the low CD8 expression group, which indicates an uneven mean distribution of lesion characteristics in the CD8 group, and thus lesion variability. This could be attributed to the fact that high numbers of CD8 cells may facilitate increased elimination of tumor cells, which results in more within-tumor heterogeneity. Further studies are warranted to confirm this.

Conclusions

CD8+ T cells are correlated with the prognosis of GBM patients. The preoperative T1C histogram is a reliable predictive tool for the levels of tumor-infiltrating CD8+ T cells in GBM; moreover, it can facilitate the preoperative prediction of the prognosis of patients with GBM.

Acknowledgements

Thanks to all the partners who contributed to this research, including Caiqiang Xue, Junlin Zhou.

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Figures

Figure 1 X-tile plot showing the association between the levels of tumor-infiltrating CD8+ T cells and survival in patients with GBM. A: The plot color represents the strength of the association for each partition, ranging from low (dark, black) to high (bright, green). Green represents a direct association. B: The optimal cutoff value for CD8+ T cells was 2.6. C: The association between CD8+ T cells and overall survival (p = 0.0156).

Figure 2 Scatter plot showing significant correlations of the CV, mean, Perc.05, Perc.10, Perc.25, and Perc.50 values with tumor-infiltrating CD8+ T cell levels.

Figure 3 A 45-year-old woman with right frontal GBM. A. The T1C map shows cystic changes within the tumor, with obvious enhancement of the cyst wall and surrounding edema; B. The method used to determine the ROI for obtaining the T1C histogram; C. The T1C histogram of the tumor mass. The T1C histogram parameter values were as follows: Minimum, 80; Maximum, 975; Mean, 2.555; SD, 1.391; Variance, 1.934; CV, 5.445; Skewness, 1.455; Perc.05, 114; Perc.10, 131; Perc.25, 169; Perc.50, 190; Perc.75, 319; D. CD8+ T cell count was 9 (HE, x 400).

Figure 4 A 54-year-old man with GBM in the right parietal lobe. A. The T1C map shows that the tumor is cystic and solid, with obvious enhancement; B. The method used to determine the ROI for obtaining the T1C histogram; C. The T1C histogram of the tumor mass. The T1C histogram values are as follows: Minimum, 130; Maximum, 836; Mean, 4.675; SD, 1.546; Variance, 2.391; CV, 3.308; Skewness, -3.427; Perc.05, 168; Perc.10, 226; Perc.25, 364; Perc.50, 484; Perc.75, 583; D. The CD8+ T cell count was 1 (HE, ×400).

Figure 5: ROC curve analysis of T1C histogram parameters to distinguish between the low and high CD8 expression groups. The predictive AUC values for CV, 1st, 5th, 10th, 25th, and 50th percentiles were 0.783, 0.662, 0.706, 0.753, 0.681, and 0.725, respectively.

Proc. Intl. Soc. Mag. Reson. Med. 31 (2023)
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DOI: https://doi.org/10.58530/2023/1961