Poster Presentation CD1-MR1 2024

Systemic activation of MAIT cells highlights their potential antitumor role in gastroesophagal adenocarcinoma (#217)

Rebecca Maltez de Sousa 1 , Itzel Medina Andrade 1 , Kejsi Zeqiraj 1 , Nora Noren 2 , Fredrik Klevebro 2 3 , Magnus Nilsson 2 3 , Niklas Björkström 1 , Andrea Ponzetta 1
  1. Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden
  2. Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
  3. Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden

The global incidence of Gastroesophageal adenocarcinoma (GEAC) has increased worldwide over the last four decades and remains the third-leading cause of mortality. The development of resistance to chemo- and radiotherapy has led to poor clinical outcomes, making GEAC a largely unmet clinical need. Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes able to mediate robust effector functions without prior antigen exposure, thus representing an attractive target for cancer therapy. However, current knowledge regarding MAIT cell anti-tumor response in GEAC is limited. Here, our aim is to provide a comprehensive view of the unconventional T cell landscape in GEAC, and to specifically characterize MAIT cells. Here we quantified the infiltration of T cell populations in peripheral blood from 15 treatment naïve GEAC patients by high dimensional flow cytometry. We observed a reduction of MAIT cells in GEAC patients as compared to healthy controls. In contrast, frequencies of other unconventional T cell populations including ɣδ T cells, iNKT cells and double negative ab T cells, remained unaltered. Circulating MAIT cells had increased CD69 surface expression, indicating an activated state. Moreover, we observed a higher proportion of Ki67 and Granzyme B in GEAC patients. While PD-1 expression was unaltered, CD39 and CD57 expression were enriched on patient MAIT cells. Interestingly, the level of MR1-5OP-RU tetramer intensity was reduced in GEAC patients compared to controls. Furthermore, soluble protein expression analysis in plasma revealed that IL-12b expression was negatively correlated with CD69 expression on MAIT cells from peripheral blood. These findings indicate a systemic activation of MAIT cells in GEAC, in line with the possible involvement of MAIT cells in GEAC antitumor immunity. Current efforts to characterize MAIT cell phenotype within the gastric mucosa is currently ongoing and may provide new insights into the role of MAIT cells in GEAC pathogenesis.