bims-maitce 2026-10-04 papers

Issue of 2026–10–04
four papers selected by
Andy E. Hogan, Maynooth University

Iran J Allergy Asthma Immunol. 2026 Aug 12. 25(Sup 11): 129-139

Immune Cell Profiling in Peptic Ulcer Disease: Investigation of MAIT Cells and Key Inflammatory Cytokines IL-17 and IFN-γ.

Alireza Omidvar-Mehrabadi, Mehdi Shakouri-Khomartash, Hasan Abedi, Mojgan Mohammadi-Mehr, Ali Faridfar, Ali Shakeri-Moghaddam.

Peptic ulcer disease (PUD) is a common gastrointestinal disorder associated with chronic mucosal inflammation and immune dysregulation. Recent evidence suggests that Mucosal-associated invariant T (MAIT) cells, a subset of T cells expressing CD161 and Vα7.2, are involved in mucosal immunity and inflammatory responses. However, their precise role in PUD remains unclear. Given their dual function in immune defense and inflammation, investigating MAIT cell alterations in PUD could provide novel insights into disease pathogenesis and potential therapeutic targets. A cross-sectional study was performed, including 25 patients with endoscopically verified PUD and 25 healthy controls. Flow cytometry was used to quantify circulating MAIT cells (Vα7.2+CD161++) and their subsets (CD4+, CD8+, and double-negative). Serum interleukin-17 (IL-17) and interferon-γ (IFN-γ) levels were measured using ELISA in 21 PUD patients and 21 healthy controls. Correlations between MAIT cell frequencies and cytokine levels were analyzed using the Spearman correlation coefficient. PUD patients exhibited a substantially elevated frequency of circulating MAIT cells compared to controls. Among subsets, CD8+ MAIT cells showed the most pronounced increase, correlating positively with serum IFN-γ levels (r=0.5819). Furthermore, levels of IL-17 and IFN-γ were substantially elevated in individuals with PUD in comparison to controls. Our results indicate that MAIT cells, particularly the CD8+ subset, may contribute to immune activation in PUD. The observed increase in MAIT cells, along with elevated IL-17 and IFN-γ levels, highlights their potential involvement in disease progression. These findings support the potential role of MAIT cells as biomarkers or therapeutic targets in PUD.

Keywords: Helicobacter pylori; Inflammation; Mucosal-associated invariant T (MAIT) cells; Peptic ulcer

DOI: https://doi.org/10.18502/ijaai.v25is11.22489

Cancer Immunol Res. 2026 Sep 28.

Immunometabolic Profiling of T Cells and Innate Lymphoid Cells Uncovers Therapeutic Targets to Enhance Immunotherapy in Head and Neck Cancer.

Sujeetha A Rajakumar, Namya Nanda, Chloe Kim, Dustin Dikeman, Tanguy Y Seiwert, Zubair Khan, Sewon Kang, Carole Fakhry, Martin P Alphonse.

Immunometabolic reprogramming governs antitumor immunity, yet its role in checkpoint blockade responses remains poorly defined. Using functional-metabolic flow cytometry, we characterized tumor-infiltrating mucosal-associated invariant T (MAIT) cells, CD8 T cells, and innate lymphoid cells (ILCs) from head and neck squamous cell carcinoma (HNSCC) patients receiving neoadjuvant anti-programmed cell death protein 1 (PD-1) monotherapy or combined anti-PD-1/anti-interleukin-8 (IL-8) therapy. We identified CD39-negative OX40 MAIT and CD8 tumor-infiltrating lymphocytes (TILs) as metabolically fit, less-exhausted populations. In contrast, OX40- cells exhibited elevated glucose-6-phosphate dehydrogenase (G6PD) expression, identifying the pentose phosphate pathway as a targetable metabolic vulnerability. Ex vivo transcriptomic analysis of CD8 TILs from untreated patients revealed CD39-stratified responses to anti-PD-1/polydatin (G6PD inhibitor) combination treatment: CD39-negative cells amplified effector programs; CD39-medium cells shifted toward lipid catabolism; and CD39-high exhausted cells showed downregulation of STAT3 and mTOR-pathway genes only under combination treatment, consistent with a shift in metabolic regulation. Secretome profiling confirmed the functional translation of this reprogramming, with combination treatment significantly increasing soluble CD27 secretion in CD39-high TILs-indicating enhanced activation in terminally exhausted populations. ILC profiling identified immunosuppressive CD294-high ILC2s, marked by elevated C-C-motif chemokine receptor 8 (CCR8) and carnitine palmitoyltransferase 1A (CPT1A) protein expression, as a potential barrier to checkpoint blockade efficacy. Conversely, CD39-negative ILC3s emerged as metabolically active populations amenable to therapeutic reprogramming. These findings establish immunometabolic profiling as a framework for guiding precision checkpoint blockade combinations in HNSCC.

DOI: https://doi.org/10.1158/2326-6066.CIR-26-0245

Microlife. 2026 ;7 uqag034

Reconstructing host-pathogen interactions: analysis of the intercellular network of macrophages and other immune cells within an aspergillosis-on-chip model.

Simranpreet Kaur, Anna Katharina Renner, Pauline Porschitz, Franziska Schmidt, Svenja Grau, Hannah Afolayan, Stanislaw Schmidt, Thomas Lehrnbecher-Lanzeni, Hubertus Haas, Axel A Brakhage, Marc Thilo Figge, Marie von Lilienfeld-Toal, Zoltan Cseresnyés, Susann Hartung, Susanne Jahreis.

The human-pathogenic fungus Aspergillus fumigatus can cause life-threatening infections, particularly in immunosuppressed or neutropenic patients with hematological malignancies. The human antifungal immune response primarily relies on neutrophils with contribution from macrophages, while the roles of unconventional lymphocytes such as Natural Killer (NK) cells and mucosal-associated invariant T (MAIT) cells remain less understood. Therefore, using an advanced microfluidic "invasive aspergillosis-on-chip" (IAC) model, we investigated the coordinated antifungal response of various immune cell types in combination with macrophages within a human tissue-like 3D environment. The IAC model, initially incorporating monocyte-derived macrophages, was enhanced by perfusing either primary neutrophils, NK cells, or MAIT cells for overnight infection experiments. In this model, hyphal growth of A. fumigatus was prevented only when both macrophages and neutrophils were present. However, uncontrolled growth was detected in neutropenic patient scenarios. We observed key interactions such as conidial shuttling and metaforosis between innate immune cells, accompanied by elevated cytokine levels of e.g. IL-1β and TNFα. Importantly, NK cells applied to the vascular compartment of the IAC model significantly reduced hyphal length, confirming their antifungal activity. Similarly, MAIT cells in sufficiently high quantities reduced hyphal growth and branching, although this effect depended on the recognition of riboflavin-derived antigens, as shown by the lack of response to the A. fumigatus ΔriboB mutant strain. Together, our findings demonstrate that the advanced IAC model is a powerful tool to dissect human antifungal immunity. The interactions observed between macrophages and other immune cells highlight the importance of multi-layered defense strategies against A. fumigatus.

Keywords: Aspergillus fumigatus; MAIT cells; NK cells; aspergillosis-on-chip model; invasive aspergillosis; neutrophils

DOI: https://doi.org/10.1093/femsml/uqag034

Front Immunol. 2026 ;17 1917317

Systematic evaluation of MAIT and iNKT abundance as checkpoint blockade biomarkers.

Yueyi Li, LinLin Chen, Shiwen Shan, Haiyang Wang, Xiaofang Xing, Jian Zhang.

Introduction: MAIT and iNKT cells are unconventional T cell lineages that bridge innate and adaptive immunity and have been implicated in antitumor immune responses and immunotherapy outcomes. However, evidence to date has largely derived from individual studies of selected cancer types or specialized immune profiling cohorts. Whether MAIT and iNKT abundance provides reproducible clinical information across large, multi-cancer immune checkpoint blockade (ICB) cohorts remains insufficiently evaluated.
Methods: We applied an AI-based TCRβ inference framework to estimate MAIT and iNKT relative abundance from bulk TCRβ repertoires in healthy controls, patients with cancer, and ICB-treated cohorts. The main dataset included 1,619 samples from 420 healthy controls and 595 patients across 13 cancer types; response analyses used a discovery cohort of 964 samples from 436 patients across 9 cancer types and an independent validation cohort of 361 samples from 81 patients across 5 cancer types.
Results: TCRβ-inferred estimates showed that both MAIT and iNKT abundance were reduced in pretreatment cancer PBMCs compared with healthy controls, supporting systemic perturbation of unconventional T cells in cancer. Abundance estimates were also tissue dependent, with MAIT showing lower inferred abundance in tumor biopsies than in PBMCs. In ICB cohorts, baseline MAIT and iNKT estimates in PBMCs or tumors were insufficient to distinguish responders from non-responders. Although on-treatment tumor iNKT estimates showed a modest enrichment in responders in the discovery cohort, this pattern had limited standalone predictive value and was not reproduced as a robust biomarker in validation.
Discusson: These findings indicate that MAIT/iNKT abundance captures cancer-associated and tissue dependent immune variation but has limited value alone for predicting ICB response, highlighting the need to incorporate functional state, spatial localization, and broader immune context.

Keywords: T cell receptor (TCR); immune checkpoint blockade (ICB); invariant natural killer T (iNKT) cells; mucosal-associated invariant T (MAIT) cells; unconventional T cells

DOI: https://doi.org/10.3389/fimmu.2026.1917317