LIMCH1 inhibits antitumor immunity by upregulating PDL1 in triple-negative breast cancer.

BACKGROUND: Breast cancer is one of the most common malignancies globally. Despite advancements in treatment, efficacy for certain subtypes such as triple-negative breast cancer (TNBC) remains limited. Immunotherapy has provided new hope for advanced breast cancer, particularly triple-negative breast cancer (TNBC), though its effectiveness varies by tumor type and patient differences. LIMCH1, a relatively understudied LIM-domain protein, has been linked to cytoskeletal regulation and various cancers, including lung, cervical, and renal carcinoma. This study aims to investigate LIMCH1 expression and its impact in breast cancer. METHODS: The prognostic role of LIMCH1 in multiple cancers was analyzed using the TCGA database, and its expression in breast cancer was validated through immunohistochemistry (IHC) on breast cancer tissue microarrays. LIMCH1 overexpression and knockdown TNBC cell lines were constructed, and CCK-8, colony formation, transwell migration, and wound healing assays were performed to assess the effect of LIMCH1 on cell proliferation and migration. PD-L1 expression and selected immune-related proteins, such as CD3, CD4, CD8, and p-ERK1/2, were evaluated by flow cytometry, immunofluorescence, or Western blotting. A mouse allograft model was established to evaluate LIMCH1’s role in tumor growth and T-cell infiltration within the TIME. RESULTS: LIMCH1 was highly expressed in breast cancer and associated with poor prognosis. Bioinformatics analysis revealed that high LIMCH1 expression correlates with an immunosuppressive state. Functional assays showed that LIMCH1 overexpression promoted proliferation and migration, while knockdown inhibited these phenotypes. Mechanistic studies indicated that LIMCH1 upregulated PD-L1 via MAPK pathway activation, suppressed CD4 + and CD8 + T-cell infiltration, and led to an immunosuppressive tumor microenvironment. High LIMCH1 expression was also linked to low response rates to anti-PD-1 therapy, suggesting it may influence immunotherapy efficacy. CONCLUSION: LIMCH1 promotes tumor activity in breast cancer by activating the MAPK pathway, upregulating PD-L1, and enhancing immune evasion. LIMCH1 may serve as a potential therapeutic target for breast cancer immunotherapy. This study provides new evidence for the role of LIMCH1 in breast cancer and offers new insights and directions for precision therapy of breast cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12964-025-02387-6.