bims-maitce 2025-10-05 papers

Issue of 2025–10–05
three papers selected by
Andy E. Hogan, Maynooth University

Neurooncol Adv. 2025 Jan-Dec;7(1):7(1): vdaf173

Characterization of MAIT cells in glioblastoma reveals a potential immunosuppressive role through a MAIT-neutrophil axis.

Background: Glioblastoma (GBM) is the most aggressive primary brain cancer in adults and remains incurable. Mucosal-associated invariant T (MAIT) cells are unconventional T cells with a semi-invariant T cell receptor and have been shown to regulate immune responses. However, the role of MAIT cells in glioblastoma (GBM) has not been well characterized.
Methods: We used flow cytometry, bulk RNA-seq and scRNA-seq, and multiplexed tissue imaging to investigate the role of MAIT cells in GBM.
Results: Flow cytometry analysis of peripheral blood samples of GBM patients showed a significant reduction of MAIT cell frequency and the ability to produce Th1 cytokines. In bulk RNA sequencing data analysis of GBM tissues, the MAIT cell gene signature significantly correlated with poor patient survival. A scRNA-seq of CD45+ cells from 20 GBM tissue samples showed 12 (60%) were positive for MAIT cells and the enrichment of RORC-expressing MAIT17. The MAIT cell signature significantly correlated with tumor-associated neutrophil (TAN) activities. Multiple immune suppressive genes known to be used by TANs were upregulated in MAIT-positive tumors. Spatial imaging analysis of GBM tissues showed that all specimens were positive for both MAIT cells and TANs, and localized enrichment of TANs.
Conclusion: These findings revealed an immunosuppressive role of MAIT cells in GBM and highlighted the MAIT-TAN axis as a potential novel therapeutic target to modulate GBM's immunosuppressive tumor microenvironment.

Keywords: MAIT cell; glioblastoma; myeloid cells; neutrophil

DOI: https://doi.org/10.1093/noajnl/vdaf173

J Immunol. 2025 Sep 30. pii: vkaf266. [Epub ahead of print]

Gastrointestinal MAIT cells in chronic HIV-1 infection.

April L Ferre, Emily A Fehrman, Peter W Hunt, Ma Somsouk, Rebecca Hoh, Michael A Eller, Dominic Paquin-Proulx, Johan K Sandberg, Barbara L Shacklett.

Mucosa-associated invariant T (MAIT) cells are innate-like T cells abundant in mucosal tissues, liver, and blood. MAIT cells recognize riboflavin metabolite-derived microbial antigens displayed by the MHC-I-related protein (MR1) and respond by producing cytokines, killing infected cells, and suppressing microbial growth. We previously demonstrated that MAIT cell numbers and function are reduced in chronic HIV-1, potentially increasing susceptibility to microbial coinfections. Here we assessed colorectal MAIT cells from people living with HIV-1 (PLWH, n = 36) and people without HIV-1 (PWOH, n = 22) by flow cytometry. In PBMCs, MAIT cells were less abundant in PLWH compared to PWOH. However, colorectal MAIT cell percentages were comparable in both groups, suggesting reduced loss from gut compared to blood in HIV-1 infection, or redistribution from blood to mucosae. In both groups, the majority of mucosal MAIT cells expressed CD8 and were enriched for CD8αα; a minority expressed CD4 or were double negative. Colorectal MAIT cells expressed CD69 and CD45RO, indicating a tissue-resident memory phenotype. Mucosal MAIT cells from PWOH expressed high perforin compared to PLWH, although granzyme B was low as compared to blood counterparts. Intracellular cytokine staining revealed robust cytokine production when stimulated with PMA/ionomycin. However, while blood MAIT cells responded strongly to inactivated Escherichia coli, mucosal MAIT cells responded poorly to this stimulus. Thus, gastrointestinal MAIT cells may be partially unresponsive toward commensal microbes, while remaining responsive to other stimuli. These findings provide novel insights into the functional profile of gastrointestinal MAIT cells in the context of chronic HIV-1.

Keywords: HIV; MAIT cells; mucosal

DOI: https://doi.org/10.1093/jimmun/vkaf266

J Exp Med. 2025 Dec 01. pii: e20250431. [Epub ahead of print]222(12):

CD2 and its ligands are involved in development and activation of MAIT cells.

Kaiwen Zhu, Jiayu Dou, Bin Li, Jin Qian, Ming-Chao Zhong, Zhenghai Tang, Yan Lu, André Veillette.

MAIT cells are innate-like T cells known for their semi-invariant TCR that recognizes vitamin B metabolites presented by MR1. While the involvement of TCR and cytokines in development and activation of MAIT cells is well documented, the contribution of co-receptors, including SLAM family receptors, remains poorly understood. This study revealed that CD2 and its ligands, CD48 in mice and CD58 in humans, were crucial for MAIT cell maturation and antigen-driven activation, but not for their responses to cytokines. Cis interactions of CD2 with its ligands on the same cell were essential for activation, with trans interactions contributing in some contexts. A natural subset of human MAIT cells lacking CD2 displayed reduced activation responses to antigen. Human CD48 recognized 2B4 rather than CD2, dampening TCR signal strength and activation of human MAIT cells. Thus, the interplay between CD2 and its ligands is pivotal for MAIT cell development and activation, highlighting potential approaches for treating human diseases implicating MAIT cells.

DOI: https://doi.org/10.1084/jem.20250431