Immunosuppressive immune microenvironment landscapes in VISTA-high gastric cancer
Menée notamment à partir de l'analyse immunohistochimique et transcriptomique d'échantillons tumoraux prélevés sur 172 patients atteints d'un cancer de l'estomac exprimant fortement la protéine VISTA, cette étude met en évidence le rôle de cette dernière dans le caractère immunosuppresseur du microenvironnement tumoral
Background : V-domain Ig-containing suppressor of T cell activation (VISTA) is an immune checkpoint molecule predominantly expressed on myeloid cells and has recently been recognised as a key mediator of immunosuppression within the tumour microenvironment (TME). However, its expression pattern in gastric cancer and the functional characteristics of the VISTA-high TME remain poorly understood.
Methods : We conducted multiplex immunohistochemistry on tumour samples from 172 patients to characterise the immune landscape of the VISTA-high tumour microenvironment. Additionally, single-cell RNA sequencing (n = 17) and spatial transcriptomics (n = 3) were employed to delineate the cellular expression patterns of VISTA and investigate the potential immunomodulatory functions of VISTA-expressing macrophages.
Results : High VISTA expression was associated with an immunosuppressive TME characterised by increased infiltration of exhausted CD8+ T cells, regulatory T cells (Tregs), M2-like macrophages, and cancer-associated fibroblasts (CAFs). Moreover, elevated VISTA levels in the tumour region were linked to worse immune-related progression-free survival (irPFS) in patients treated with immune checkpoint inhibitors (ICIs). Mechanistically, VISTA+ monocyte-macrophage (MoMac) populations promoted T cell exhaustion via the LGALS9-PTPRC signalling axis and exhibited enhanced antigen-presenting capacity.
Conclusions : Our findings establish VISTA as a central immunoregulatory checkpoint in gastric cancer, suggesting its potential as a promising therapeutic target for combination immunotherapeutic approaches.
British Journal of Cancer , article en libre accès, 2026