Abstract
The effect of chemotherapies on the crosstalk interaction between CD8 cytotoxic T-cells and MHC-I peptides in the microenvironment of WHO grade 4 astrocytoma
- Department of Pathology, Faculty of Medicine, King Abdulaziz University, Rabigh, Saudi Arabia
- Department of Surgery, King Abdulaziz University Hospital, Jeddah, Saudi Arabia
- Department of Neurosurgery, King Fahad General Hospital, Madinah, Saudi Arabia
- Department of Pathology, College of Medicine, Umm Al-Qura University, Mecca, Saudi Arabia
- Department of Neurosurgery, King Fahad General Hospital, Jeddah, Saudi Arabia
- Department of Clinical Physiology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
- Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
- Department of Laboratory of Translation Neuroscience, CEINGE, Biotecnologie Avanzate, Naples, Italy
- Department of Neuroscience, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia
- Department of Pediatrics, King Abdulaziz University and Hospital, Jeddah, Saudi Arabia
- Department of Internal Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
- Department of Surgery, Faculty of Medicine, University of Tabuk, Tabuk, Saudi Arabia
Introduction:
CD8+ T-cells and MHC-I have been detected in brain gliomas with a significant outcome. The effect of chemotherapies on the crosstalk interaction between CD8+ T-cells and MHC-I has never been explored.
Material and methods:
The protein expression profiling of CD8 cytotoxic T-cells and the gene expression assay of MHC-I in 35 patients diagnosed with WHO grade 4 astrocytoma were performed. The impact of these two factors on tumor recurrence was analyzed.
Results:
IDH was wildtype in 13 tumors. MHC-I protein expression was absent or low in 34 tumors and dense in a single case. MHC-I gene expression was upregulated in 10 tumors and 25 tumors showed MHC-I gene downregulation. Temozolomide (TMZ) was given to 24 patients and 11 patients received TMZ plus other chemotherapies. No statistically significant association was observed between IDH mutation and CD8+ T-cells (p = 0.383). However, this association was significant in recurrence-free interval (RFI) (p = 0.012). IDH-wildtype tumors with highly infiltrated CD8+ T-cells or IDH-mutant tumors with low CD8+ T-cells showed late tumor recurrence. There was a statistically significant difference in RFI between tumors with different MHC-I expression and CD8+ T-cell counts after treatment with TMZ or TMZ plus (p = 0.026).
Conclusions:
No association between IDH mutation and CD8+ cytotoxic T-cell was found. IDH is directly linked to tumor recurrence regardless of CD8+ T-cells infiltration. TMZ plus other adjuvants is proved to be more effective in improving patient survival and delaying tumor recurrence, as compared to using TMZ alone. Nonetheless, none-TMZ adjuvants may increase tumor sensitization to cytotoxic T-cells more than TMZ.
Keywords
WHO grade 4 astrocytoma, MHC-I, CD8, chemotherapies, recurrence
Integrated with
