Background & Aims Gallbladder cancer (GBC) has a high risk of postoperative recurrence, and immunotherapy-based adjuvant approaches remain unstandardised. We aimed to define spatial immunophenotypes in GBC and evaluate their associations with clinical outcomes and immune-evasion mechanisms. Methods We used multiplex immunohistochemistry to quantify 16 immune-cell subsets across the tumour core, tumour margin and peritumour regions in 86 treatment-na & iuml;ve GBCs, and integrated nerve bundle-centred spatial analysis with transcriptomic profiling (n = 9) to investigate perineural invasion (PNI)-associated immune-evasion mechanisms. Results Unsupervised clustering and a CD8/alpha-SMA dual-marker approach defined three spatial immunophenotypes: immune-inflamed, immune-excluded, and immune-desert. The immune-inflamed phenotype featured high intratumoural immune infiltration with elevated PD-L1 expression (median combined positive score: 13.85 vs. 0.41 vs. 0.25, p <0.001), was associated with better prognosis (overall survival [OS]: hazard ratio [HR] 0.25, 95% CI 0.12-0.54, p <0.001; recurrence-free survival [RFS]: HR 0.41, 95% CI 0.21-0.79, p = 0.008), and improved outcomes with adjuvant chemoimmunotherapy vs. chemotherapy alone (OS: HR 0.10, 95% CI 0.02-0.48, p <0.001; RFS: HR 0.29, 95% CI 0.12-0.70, p = 0.003). The immune-excluded phenotype was stroma-enriched (alpha-SMA, p <0.001), with immune cells largely restricted to the tumour margin or peritumour regions; the immune-desert phenotype showed sparse immune infiltration. PNI was associated with immunosuppressive chronic inflammation, characterised by enrichment of PD-L1(+) myeloid cells and exhausted CD8(+) T cells near invaded nerve bundles (cell density, p <0.001). Transcriptomic analyses suggested enhanced tumour neurotropism in PNI-positive tumours (gene-set enrichment, p <0.05), together with activation of IL-6/IGF-1 related chronic inflammatory signalling and lipid-metabolic rewiring involving LEP, CD36, and ADIPOQ, collectively shaping a local immune-evasion niche (FDR <0.05). Conclusions We defined three spatial immunophenotypes in GBC with distinct immune features and clinical outcomes. PNI was associated with the formation of a local immune-evasion niche. (c) 2026 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).