bims-maitce 2025-05-11 papers

Issue of 2025–05–11
two papers selected by
Andy E. Hogan, Maynooth University

Front Immunol. 2025 ;16 1553034

Patient-derived pancreatic tumor bacteria exhibit oncogenic properties and are recognized by MAIT cells in tumor spheroids.

Poojabahen Tajpara, Michał Jacek Sobkowiak, Katie Healy, Sabrina Naud, Beate Gündel, Asif Halimi, Zara Ahmad Khan, Giorgio Gabarrini, Sylvie Le Guyader, Gabriela Imreh, Julie A Reisz, Marco Del Chiaro, Angelo D'Alessandro, Rainer Heuchel, J Matthias Löhr, Volkan Özenci, Margaret Sällberg Chen.

Introduction: Tumor-residing microbiota poses a new challenge in cancer progression and therapy; however, the functional behavior of patient tumor-derived microbes remains poorly understood. We previously reported the presence of tumor microbiota in intraductal papillary mucinous neoplasms (IPMNs), which are precursors of pancreatic cancer.
Methods: We examined the metabolic and pathogenic potential of clinical microbiota strains obtained from IPMN tumors using various pancreatic cell lines and 3D spheroid models.
Results: Our findings revealed that several strains from IPMNs with invasive cancer or high-grade dysplasia, such as E. cloacae, E. faecalis, and K. pneumoniae, induced a cancer metabolite signature in human pancreatic cells when infected ex vivo. Bacterial invasiveness was significantly correlated with DNA damage in spheroids derived from normal and tumor-derived pancreatic cells, particularly in strains derived from advanced neoplasia IPMN and under hypoxic conditions. Additionally, microbial metabolites activate human mucosal-associated invariant T (MAIT) cells and restrict the infection, both extra- and intracellularly, in hypoxic tumor conditions and in synergy with antibiotics.
Discussion: Immune sensing of tumor microbiota metabolites may have clinical implications in cancer management.

Keywords: DNA damage; MAIT cells; immunotherapy; metabolites; pancreatic neoplasm; spheroids; tumor microbiota

DOI: https://doi.org/10.3389/fimmu.2025.1553034

Immunol Rev. 2025 May;331(1): e70033

Molecular Insights Into MR1-Mediated T Cell Immunity: Lessons Learned and Unanswered Questions.

Wael Awad, Mohamed R Abdelaal, Victoria Letoga, James McCluskey, Jamie Rossjohn.

The major histocompatibility complex class-I related protein, MR1, is an evolutionarily conserved antigen presenting molecule that binds and displays organic metabolites to T cells, including mucosal associated invariant T (MAIT) cells and diverse MR1-restricted T cells (MR1T). Structural studies have elucidated how MR1 can accommodate a range of chemical scaffolds that arise from foreign, synthetic, and self-metabolites, although the full spectrum of metabolites that MR1 presents remains unclear. Presently, MAIT and MR1T cell recognition of MR1-antigen complexes represents a new immune recognition paradigm and is emerging as a critical player in protective immunity, aberrant immunity, tumor immunity, and tissue repair. Moreover, the limited allelic variation of MR1 makes it an attractive therapeutic target. This review will address the unique features and capability of the MR1 molecule to display several classes of small molecules for T cell surveillance. We will also address the molecular basis underlying MAIT and MR1T TCR recognition of MR1-binding ligands.

Keywords: MAIT and MR1‐restricted T cells and structural immunology; MR1; metabolite antigens

DOI: https://doi.org/10.1111/imr.70033