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

化疗对 WHO 4 级星形细胞瘤微环境中 CD8 细胞毒性 T 细胞与 MHC-I 肽之间串扰相互作用的影响

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作者:Nadeem Butt, Maryam Enani, Maryam Alshanqiti, Alaa Alkhotani, Taghreed Alsinani, Mohammed Matoog Karami, Motaz M Fadul, Majid Almansouri, Amber Hassan, Saleh Baeesa, Ahmed K Bamaga, Shadi Alkhayyat, Eyad Faizo, Maher Kurdi

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.

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.

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.

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