The Pathological Evaluation of Autophagy-Related Protein (LC3B) and Its Association with the Infiltration of Immune Cells in Glioma

Abstract

Background: Tumor cell autophagy can influence cellular immunity by participation in the recognition and modification of tumor-related antigens. Objectives: The objective of this study was to evaluate the immunohistochemical expression of the autophagy-related marker; light chain 3B (LC3B) in tumor cells and the assessment of T lymphocytes by a cluster of differentiation 3 (CD3) in gliomas, and to correlate them with the available clinic-pathological variables in glioma patients. Materials and methods: Immunohistochemical staining for LC3B and CD3 was performed on 60 paraffin-embedded glioma tissue. LC3B immunoreactivity score of 0-6 was designated negative, and those scoring 7-12 were considered positive. The median level of CD3 positive T lymphocytes was calculated for both high and low-grade gliomas. In low-grade gliomas, the CD3 expressing T lymphocytes equal to or more than 2.6, were considered positive while in high-grade gliomas, those equal to or more than 16 were considered positive. Results: LC3B expression in tumor cells was detected in 24/60 (40%) of gliomas. Expression of LC3B was significantly more frequent in high-grade gliomas (23/33, 69.7%) compared to low grade ones (1/27, 5%), (p value= 0.000). LC3B expression was correlated with the patients age (P value= 0.047) & histological variants (P value= 0.000). CD3 positive T lymphocytes were significantly more prominent in high-grade gliomas (25/33 , 41.7%) than low-grade ones (2/27, 3.3%), (P value= 0.001). A significant association was noted between CD3 expression and the patients age (P value= 0.003), sex (P value: 0.035) and histological variants (P value= 0.001). LC3B expression in tumor cells was significantly correlated with CD3 positive T lymphocytes (P value: 0.000). Conclusion: Autophagic activity of tumor cells and T lymphocyte infiltrates were reported more in high-grade gliomas compared to low-grade ones, giving high-grade gliomas the chance in autophagy target therapy & immunotherapy.

Investigating the Association between the Autophagy Markers LC3B, SQSTM1/p62, and DRAM and Autophagy-Related Genes in Glioma

“…Similarly, out of the 20 strongly positive cases of SQSTM1/p62 , none were found in the LGG category, and this difference achieved statistical significance (as indicated in Table 3 ). These results are in accordance with other studies, which reported that LC3B and SQSTM1/p62 were highly expressed in high-grade gliomas [ 29 , 30 , 31 ]. Remarkably, there is a statistically significant association between the autophagy markers LC3B and SQSTM1/p62 ( p = 0.000), highlighting the interaction between them.…”

Investigating the Association between Autophagy Markers LC3B, P62, DRAM and Autophagy-Related Genes in Glioma

“…Similarly, out of the 20 strongly positive cases of SQSTM1/p62, none was found in the LGG category, and this difference achieved statistical significance (as indicated in Table 3). These results were in accordance with other studies which reported that LC3B and SQSTM1/p62 was highly expressed in high grade gliomas [29][30][31]. Remarkably there is statistically significant association between the autophagy markers LC3B and SQSTM1/p62 (p=0.000), highlighting the interaction among each other.…”