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Article

Overexpression of Potential Markers of Regulatory and Exhausted CD8+ T Cells in the Peripheral Blood Mononuclear Cells of Patients with B-Acute Lymphoblastic Leukemia

by
Mahdieh Naghavi Alhosseini
,
Marianna Palazzo
,
Luigi Cari
,
Simona Ronchetti
*,
Graziella Migliorati
and
Giuseppe Nocentini
Pharmacology Division, Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2023, 24(5), 4526; https://doi.org/10.3390/ijms24054526
Submission received: 9 February 2023 / Revised: 20 February 2023 / Accepted: 21 February 2023 / Published: 24 February 2023
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)

Abstract

B-acute lymphoblastic leukemia (B-ALL) is one of the most common pediatric cancers, wherein regulatory T cells (Treg) and exhausted CD8+ T cells may be important in its development and maintenance. In this bioinformatics study, we evaluated the expression of 20 Treg/CD8 exhaustion markers and their possible roles in patients with B-ALL. The mRNA expression values of peripheral blood mononuclear cell samples from 25 patients with B-ALL and 93 healthy subjects (HSs) were downloaded from publicly available datasets. Treg/CD8 exhaustion marker expression was normalized with that of the T cell signature and correlated with the expression of Ki-67, regulatory transcription factors (FoxP3, Helios), cytokines (IL-10, TGF-β), CD8+ markers (CD8α chain, CD8β chain), and CD8+ activation markers (Granzyme B, Granulysin). The mean expression level of 19 Treg/CD8 exhaustion markers was higher in the patients than in the HSs. In patients, the expression of five markers (CD39, CTLA-4, TNFR2, TIGIT, and TIM-3) correlated positively with Ki-67, FoxP3, and IL-10 expression. Moreover, the expression of some of them correlated positively with Helios or TGF-β. Our results suggested that Treg/CD8+ T cells expressing CD39, CTLA-4, TNFR2, TIGIT, and TIM-3 favor B-ALL progression, and targeted immunotherapy against these markers could be a promising approach for treating B-ALL.
Keywords: B-acute lymphoblastic leukemia; Treg markers; CD8 exhaustion markers B-acute lymphoblastic leukemia; Treg markers; CD8 exhaustion markers

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MDPI and ACS Style

Naghavi Alhosseini, M.; Palazzo, M.; Cari, L.; Ronchetti, S.; Migliorati, G.; Nocentini, G. Overexpression of Potential Markers of Regulatory and Exhausted CD8+ T Cells in the Peripheral Blood Mononuclear Cells of Patients with B-Acute Lymphoblastic Leukemia. Int. J. Mol. Sci. 2023, 24, 4526. https://doi.org/10.3390/ijms24054526

AMA Style

Naghavi Alhosseini M, Palazzo M, Cari L, Ronchetti S, Migliorati G, Nocentini G. Overexpression of Potential Markers of Regulatory and Exhausted CD8+ T Cells in the Peripheral Blood Mononuclear Cells of Patients with B-Acute Lymphoblastic Leukemia. International Journal of Molecular Sciences. 2023; 24(5):4526. https://doi.org/10.3390/ijms24054526

Chicago/Turabian Style

Naghavi Alhosseini, Mahdieh, Marianna Palazzo, Luigi Cari, Simona Ronchetti, Graziella Migliorati, and Giuseppe Nocentini. 2023. "Overexpression of Potential Markers of Regulatory and Exhausted CD8+ T Cells in the Peripheral Blood Mononuclear Cells of Patients with B-Acute Lymphoblastic Leukemia" International Journal of Molecular Sciences 24, no. 5: 4526. https://doi.org/10.3390/ijms24054526

APA Style

Naghavi Alhosseini, M., Palazzo, M., Cari, L., Ronchetti, S., Migliorati, G., & Nocentini, G. (2023). Overexpression of Potential Markers of Regulatory and Exhausted CD8+ T Cells in the Peripheral Blood Mononuclear Cells of Patients with B-Acute Lymphoblastic Leukemia. International Journal of Molecular Sciences, 24(5), 4526. https://doi.org/10.3390/ijms24054526

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