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

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

doi:10.5114/fn.2023.131014

eISSN: 1509-572x
ISSN: 1641-4640

Folia Neuropathologica

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3/2023
vol. 61

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abstract:

Original paper

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

Nadeem Butt

¹

,

Maryam Enani

²

,

Maryam Alshanqiti

³

,

Alaa Alkhotani

⁴

,

Taghreed Alsinani

⁵

,

Mohammed Matoog Karami

⁶

,

Motaz M Fadul

¹

,

Majid Almansouri

⁷

,

Amber Hassan

⁸

,

Saleh Baeesa

⁹

,

Ahmed K Bamaga

¹⁰

,

Shadi Alkhayyat

¹¹

,

Eyad Faizo

¹²

,

Maher Kurdi

¹

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

Folia Neuropathol 2023; 61 (3): 317-325

DOI: https://doi.org/10.5114/fn.2023.131014

Online publish date: 2023/09/06

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AMA

Butt N, Enani M, Alshanqiti M, et al. 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. Folia Neuropathologica. 2023;61(3):317-325. doi:10.5114/fn.2023.131014.

APA

Butt, N., Enani, M., Alshanqiti, M., Alkhotani, A., Alsinani, T.,  & Karami, M. et al. (2023). 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. Folia Neuropathologica, 61(3), 317-325. https://doi.org/10.5114/fn.2023.131014

Chicago

Butt, Nadeem, Maryam Enani, Maryam Alshanqiti, Alaa Alkhotani, Taghreed Alsinani, Mohammed Matoog Karami,  and Motaz M Fadul et al. 2023. "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". Folia Neuropathologica 61 (3): 317-325. doi:10.5114/fn.2023.131014.

Harvard

Butt, N., Enani, M., Alshanqiti, M., Alkhotani, A., Alsinani, T., Karami, M., Fadul, M., Almansouri, M., Hassan, A., Baeesa, S., Bamaga, A., Alkhayyat, S., Faizo, E.,  and Kurdi, M. (2023). 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. Folia Neuropathologica, 61(3), pp.317-325. https://doi.org/10.5114/fn.2023.131014

MLA

Butt, Nadeem et al. "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." Folia Neuropathologica, vol. 61, no. 3, 2023, pp. 317-325. doi:10.5114/fn.2023.131014.

Vancouver

Butt N, Enani M, Alshanqiti M, Alkhotani A, Alsinani T, Karami M et al. 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. Folia Neuropathologica. 2023;61(3):317-325. doi:10.5114/fn.2023.131014.

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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:

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

Nadeem Butt 1 , Maryam Enani 2 , Maryam Alshanqiti 3 , Alaa Alkhotani 4 , Taghreed Alsinani 5 , Mohammed Matoog Karami 6 , Motaz M Fadul 1 , Majid Almansouri 7 , Amber Hassan 8 , Saleh Baeesa 9 , Ahmed K Bamaga 10 , Shadi Alkhayyat 11 , Eyad Faizo 12 , Maher Kurdi 1

WHO grade 4 astrocytoma, MHC-I, CD8, chemotherapies, recurrence