bims-maitce 2026-02-01 papers

Issue of 2026–02–01
four papers selected by
Andy E. Hogan, Maynooth University

Neurol Neuroimmunol Neuroinflamm. 2026 Mar;13(2): e200546

Brain-Resident MAIT Cells Infiltrate GL261 Tumors, and Activated MAIT Cell Signatures Are Associated With Improved Outcomes in Glioma.

Eleanor M Eddy, Md Abdullah Al Kamran Khan, Timothy Patton, Davide Moi, Huimeng Wang, Jeremy P Le, Michael N T Souter, Adam G Nelson, Phoebe M Dewar, Shihan Li, James McCluskey, Roberta Mazzieri, Riccardo Dolcetti, Zhenjun Chen, Alexander D Barrow, Alexandra J Corbett.

BACKGROUND AND OBJECTIVES: Mucosal-associated invariant T (MAIT) cells are unconventional T cells with emerging roles in antitumor immunity. Their phenotype in the brain and potential role in immunity to gliomas-including lower-grade (WHO grades I and II) and higher-grade gliomas such as grades III and IV (glioblastoma)-remain poorly defined.
METHODS: We assessed the role of MAIT cells in glioma using publicly available transcriptomic data from patient cohorts. We then characterized MAIT cells in the mouse brain using flow cytometry and assessed their impact on survival and on other immune cells in the murine GL261 model of high-grade glioma. We tested previously developed methods to activate and expand MAIT cells in mice for their effect on brain MAIT cells.
RESULTS: Analysis of The Cancer Genome Atlas revealed an association between a gene signature of activated, but not naïve, MAIT cells and improved survival in patients with grade III glioma. In mice, MAIT cells were predominantly brain-resident and infiltrated GL261 tumors where they produced IL-17 and IFN-γ. Notably, MAIT cell-deficient Mr1-/- mice displayed reduced survival after GL261 tumor induction, suggesting a protective role for MAIT cells in higher grade gliomas. Injection of MAIT antigen and adjuvants expanded brain-resident MAIT cells, but expansion of MAIT cells alone prior to GL261 tumor induction did not significantly alter survival.
DISCUSSION: Overall, this study supports a protective role for a population of brain-resident MAIT cells in glioma and highlights their potential involvement in immune surveillance of the CNS. Our findings also lay a foundation to explore the therapeutic modulation of MAIT cells in the brain.

DOI: https://doi.org/10.1212/NXI.0000000000200546

J Leukoc Biol. 2026 Jan 28. pii: qiag014. [Epub ahead of print]

Tracing MR1 expression across tissues to find the perfect MAIT.

Christy H Clutter, Daniel T Leung.

Mucosal associated invariant T (MAIT) cells are part of a T cell subset that is activated upon presentation of B2 vitamin (riboflavin) metabolites by the major histocompatibility complex, class I related (MR1) protein. Though there is a clear relationship between microbial production of riboflavin and MAIT cell development and persistence, little is known about the cells that primarily communicate with MAIT cells and other MR1-restricted T cells. Elegant work by Deng et al demonstrates that it is macrophages from the lung and peritoneum that express the highest amount of MR1 and are the most efficient at presenting vitamin B antigens to MAIT cells. This landmark study not only definitively identifies and maps the key antigen presenting cell populations involved in MAIT cell activation, it also reveals a bidirectional relationship between MR1 expression and the host microbiome. While further work on how these findings translate to human MAIT cell biology is needed, this study has provided us with unprecedented insights into the mechanistic interplay and microbial ecology of MR1 presentation of riboflavin metabolites.

Keywords: MR1; Mucosal associated invariant T (MAIT) cells; antigen presentation

DOI: https://doi.org/10.1093/jleuko/qiag014

Int J Mol Sci. 2026 Jan 10. pii: 715. [Epub ahead of print]27(2):

Spatial Imbalance of Innate-like T-Cell Niches Underlies Clinical Trajectories in Psoriasis.

Caio Santos Bonilha.

Innate-like T cells (iLTCs) are rapid sentinels at epithelial surfaces, yet their spatial organisation and tissue-linked programmes in psoriatic inflammation remain incompletely defined. Spatial transcriptomics from independent cohorts maps γδT and mucosal-associated invariant T cells (MAIT) niches across psoriatic skin and reveals sharply divergent skin-layer arrangements. Psoriatic plaques show expansion of both niches, with γδT transcriptional signatures present in dermis and epidermis and MAIT signatures strongly enriched in the epidermis. Their compartment-specific positioning is mirrored by distinct transcriptional activities that support dermal-sentinel behaviour for γδT-enriched niches and epithelial-retention programmes for MAIT niches. Clinical severity associates with opposite niche dynamics, marked by decreasing dermal γδT frequencies and increasing epidermal MAIT abundance. Functional profiles reinforce this divergence, as dermal γδT niches display rising exhaustion-associated features with greater severity, whereas epidermal MAIT niches show stronger inflammatory and proliferation-related signals. Peripheral CITE-seq profiling identifies parallel systemic patterns, with reduced γδT frequencies and increased MAIT frequencies in blood, along with exhaustion-associated features in γδT cells and MAIT-specific trafficking cues that align with their behaviour in psoriatic tissue. Together the findings define a spatially imbalanced γδT-MAIT axis in psoriatic inflammation that is linked to layer-specific organisation to local inflammatory cues, systemic immune engagement and clinical severity.

Keywords: MAIT cell; autoimmune disease; iLTC; spatial transcriptomics; γδ T cell

DOI: https://doi.org/10.3390/ijms27020715

Front Immunol. 2025 ;16 1691743

From innate-like to innate: the next wave of off-the-shelf CAR immunotherapies.

Ying Feng, Zhibo Yang, Yueru Zhou, Ying Liang, Hai Zhao.

While autologous CAR T-cell therapies have revolutionized the treatment of hematologic malignancies, their widespread application is hindered by manufacturing complexities, high costs, and limited efficacy against solid tumors due to antigen heterogeneity and the TME. Moreover, the logistical burden of bespoke patient-specific manufacturing restricts global scalability. In response, the immunotherapy landscape is pivoting toward "off-the-shelf" allogeneic therapies derived from innate and innate-like effectors. This review provides a comprehensive analysis of four emerging platforms: CAR-NK cells, CAR-NKT cells, γδ T cells, and CAR-M. Unlike conventional αβ T cells, these lineages utilize MHC-independent mechanisms to recognize stress-induced ligands or lipid antigens, inherently minimizing the risk of GvHD while enabling standardized, batched manufacturing. We critically examine the diverse manufacturing paradigms, contrasting the scalability of iPSC-derived sources with the accessibility of umbilical cord blood products. Furthermore, we detail advanced engineering strategies designed to overcome the lineage-specific limitations revealed by early trials-specifically, "armoring" constructs with IL-15 to boost in vivo persistence and metabolic reprogramming to sustain function within the TME. Finally, we synthesize emerging clinical evidence which confirms the favorable safety profile of these allogeneic approaches but highlights persistent bottlenecks: limited durability of response, cryopreservation-induced loss of viability, and batch-to-batch variability. We conclude that unlocking the full potential of innate CAR therapies requires a dual focus on harmonizing manufacturing controls and developing next-generation engineering logic to ensure durable control of solid tumors.

Keywords: CAR-NK; CAR-iNKT; CAR-macrophage; CAR-γδ T; IL-15 armoring; IPSC; Keywords: allogeneic; MAIT

DOI: https://doi.org/10.3389/fimmu.2025.1691743