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Background Butyrophilin 1A1 (BTN1A1) is increasingly recognized as a novel immunoregulatory molecule with potential utility as a biomarker in cancer immunotherapy. While previous studies have demonstrated BTN1A1’s role in modulating T cell activity through interaction with Galectin-9, its relationship with immune cell infiltration in the tumor microenvironment (TME) remains incompletely understood.Methods We utilized the multiplexed imaging platform CellDIVE™ to analyze tissue microarrays (TMAs) from patients with lung and colon cancer. A panel of 12 markers—including BTN1A1, Ki-67, PanCK, and immune cell markers for CD4 + and CD8+ T cells, monocytes (CD68+), and regulatory T cells (FOXP3+)—was used to assess immune cell distribution and phenotype. BTN1A1 expression was quantitatively measured and spatially mapped in relation to immune cell localization.Results Tumor samples with high BTN1A1 expression exhibited a significant reduction in intratumoral CD8 + T cell infiltration. Spatial analysis further revealed that CD8+ T cells were located at greater distances from BTN1A1-high tumor regions, suggesting impaired cytotoxic immune engagement. In contrast, the levels and spatial distribution of CD4+ T cells, CD68+ monocytes/macrophages, and FOXP3+ regulatory T cells showed no consistent differences between BTN1A1-high and BTN1A1-low tumors.Conclusions These findings indicate that elevated BTN1A1 expression may restrict cytotoxic T cell infiltration, contributing to an immunologically ‘cold’ tumor microenvironment. While its impact on other immune subsets appears limited, the inverse association with CD8 + T cells positions BTN1A1 as a candidate immune evasion marker. Accordingly, BTN1A1 may serve as both a stratification biomarker and a therapeutic target, particularly in the context of ongoing clinical development of anti-BTN1A1 antibody-based immunotherapies.