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

• Published in: Folia neuropathologica Vol. 61; no. 3; pp. 317 - 325
• Main Authors: Butt, Nadeem, Enani, Maryam, Alshanqiti, Maryam, Alkhotani, Alaa, Alsinani, Taghreed, Karami, Mohammed Matoog, Fadul, Motaz M, Almansouri, Majid, Hassan, Amber, Baeesa, Saleh, Bamaga, Ahmed K, Alkhayyat, Shadi, Faizo, Eyad, Kurdi, Maher
• Format: Journal Article
• Language: English
• Published: Warsaw Termedia sp. z o.o 01-01-2023; Termedia Publishing House
• Subjects: Adjuvants; Astrocytoma; Brain tumors; cd8; CD8 antigen; Cell survival; chemotherapies; Chemotherapy; Cytotoxicity; Gene expression; Glioma cells; Lymphocytes T; Metastases; mhc-i; Microenvironments; Mutation; Protein expression; recurrence; Statistical analysis; Temozolomide; Tumors; who grade 4 astrocytoma
• ISSN: 1641-4640; 1509-572X
• DOI: 10.5114/fn.2023.131014

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.