bims-maitce 2025-08-31 papers

Issue of 2025–08–31
three papers selected by
Andy E. Hogan, Maynooth University

J Am Heart Assoc. 2025 Sep 02. 14(17): e039878

Circulating Mucosal-Associated Invariant T Cells Are Associated With Acute Human Ischemic Stroke and Predict Poor Outcome.

Tadashi Ozawa, Asako Chiba, Hiroko Hayakawa, Tsukasa Ohmori, Sachiko Miyake, Shigeru Fujimoto, Ryota Tanaka.

BACKGROUND: Mucosal-associated invariant T (MAIT) cells are involved in acute ischemic stroke in mice models. This study aimed to clarify the dynamics and role of circulating MAIT cells in patients with acute ischemic stroke.
METHODS: Patients with acute ischemic stroke were classified according to the National Institutes of Health Stroke Scale into severe (score ≥ 10) and mild (score < 10) groups; outpatients with matched sex and age were selected as controls. Circulating MAIT cells, activation (CD69+), and cytokine production (IFN-γ [interferon-gamma] + and IL-17 [interleukin-17]+) on days 3, 10, and 17 after stroke, along with invariant natural killer T cells, gamma delta T cells, CD4+, and CD8+ T-cell populations, were analyzed by flow cytometry. The relationship between MAIT cell dynamics and clinical outcomes was examined.
RESULTS: One hundred participants (30 severe, 40 mild, 30 controls) were included. On day 3, patients with severe stroke had a significantly lower proportion of MAIT cells than the mild group and controls (severe, mild, control [median]: 0.09%, 0.33%, 0.38%, respectively; P < 0.001), which gradually recovered on day 17. Severe stroke MAIT cells showed higher frequencies of CD69 expression and IL-17 production. Multivariate analysis showed patients in the lowest MAIT cell population quartile on day 3 had a significantly higher probability of poor outcomes at 3 months than those in the highest quartile (odds ratio, 21.64 [95% CI, 1.41-331.58]; P = 0.027).
CONCLUSIONS: An early decrease in MAIT cells with higher activity and proinflammatory cytokine production correlated with stroke severity and poor outcomes, suggesting a significant role of MAIT cells in acute cerebral infarction and unfavorable outcomes.

Keywords: gamma delta T cells; invariant natural killer T cell; ischemic stroke; mucosal‐associated invariant T cell; poor outcome

DOI: https://doi.org/10.1161/JAHA.124.039878

Pharmaceuticals (Basel). 2025 Aug 04. pii: 1154. [Epub ahead of print]18(8):

Unconventional Immunotherapies in Cancer: Opportunities and Challenges.

Meshael Alturki, Abdullah A Alshehri, Ahmad M Aldossary, Mohannad M Fallatah, Fahad A Almughem, Nojoud Al Fayez, Majed A Majrashi, Ibrahim A Alradwan, Mohammad Alkhrayef, Mohammad N Alomary, Essam A Tawfik.

Conventional immunotherapy, including immune checkpoint blockade and chimeric antigen receptor (CAR)-T cells, has revolutionized cancer therapy over the past decade. Yet, the efficacy of these therapies is limited by tumor resistance, antigen escape mechanisms, poor persistence, and T-cell exhaustion, particularly in the treatment of solid tumors. The emergence of unconventional immunotherapies offers novel opportunities by leveraging diverse immune cell subsets and synthetic biologics. This review explores various immunotherapy platforms, including gamma delta T cells, invariant natural killer T cells, mucosal-associated invariant T cells, engineered regulatory T cells, and universal CAR platforms. Additionally, it expands on biologics, including bispecific and multispecific antibodies, cytokine fusions, agonists, and oncolytic viruses, showcasing their potential for modular engineering and off-the-shelf applicability. Distinct features of unconventional platforms include independence from the major histocompatibility complex (MHC), tissue-homing capabilities, stress ligand sensing, and the ability to bridge adaptive and innate immunity. Their compatibility with engineering approaches highlights their potential as scalable, efficient, and cost-effective therapies. To overcome translational challenges such as functional heterogeneity, immune exhaustion, tumor microenvironment-mediated suppression, and limited persistence, novel strategies will be discussed, including metabolic and epigenetic reprogramming, immune cloaking, gene editing, and the utilization of artificial intelligence for patient stratification. Ultimately, unconventional immunotherapies extend the therapeutic horizon of cancer immunotherapy by breaking barriers in solid tumor treatment and increasing accessibility. Continued investments in research for mechanistic insights and scalable manufacturing are key to unlocking their full clinical potential.

Keywords: MAIT cells; bispecific antibodies; iNKT cells; immune engineering; synthetic biology; unconventional immunotherapy; γδ T cells

DOI: https://doi.org/10.3390/ph18081154

Sci Transl Med. 2025 Aug 27. 17(813): eadq7985

Immune response and clinical severity are shaped by skin-adapted Staphylococcus aureus in chronically infected patients.

Despite the well-described association of skin lesions with Staphylococcus aureus, the distinct ability of clinical isolates to influence the local and systemic inflammatory response in a patient-specific manner is insufficiently characterized. In this study, we analyzed clinical recessive dystrophic epidermolysis bullosa (RDEB), which is characterized by wounds chronically colonized with S. aureus, to explore the relationship between inflammatory immune response and strain diversity. Children with RDEB (moderate phenotype, n = 5; severe phenotype, n = 10) and controls (n = 18) were enrolled in the study. Profiling of plasma proteins (n = 800), immune cells (n = 30 subsets and cytokine-producing cells), and cytokines (n = 38) identified a specific inflammatory signature in severe disease. Furthermore, patients with severe RDEB presented a high frequency of interleukin-17A+ (IL-17A+) cells among CD4+ and mucosal-associated invariant T (MAIT) lymphocytes. Positive S. aureus cultures from the skin of patients with RDEB allowed whole-genome sequencing of patient strains and assessment of primary keratinocyte immune response upon bacterial challenge. S. aureus secretome and conditioned medium from keratinocytes challenged with S. aureus strains from patients with severe but not from those with moderate RDEB promoted strong activation and a pro-IL-17 response in both CD4+ and MAIT cells. Our findings show that S. aureus strains isolated from patients with severe RDEB induce an IL-17-skewed immune response and pave the way for precision microbiology to explain and predict the highly variable virulence potential of bacterial clinical isolates.

DOI: https://doi.org/10.1126/scitranslmed.adq7985