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Archive > Volume 33 Issue 6 > 2026,33(6):641-650. DOI:10.3872/j.issn.1007-385X.2026.06.006 Prev Next
Basic Research
Live attenuated measles， mumps and rubella vaccine induces immunogenic cell death to activate anti-tumor immunity in triple-negative breast cancer
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Abstract:
[Abstract] Objective: To investigate the immunomodulatory mechanisms of the live attenuated measles, mumps and rubella vaccine (MMR) against triple-negative breast cancer (TNBC) via induction of immunogenic cell death (ICD). Methods: In vitro experiments: The CCK-8 assay was used to evaluate the effect of MMR on the viability of TNBC cell lines 4T1 and MDA-MB-231. Immunofluorescence was performed to detect the expression of calreticulin (CALR) in MDA-MB-231 cells. ATP was measured using a phosphomolybdic acid colorimetric assay, and high mobility group box 1 (HMGB1) levels in the cell supernatant were determined by ELISA. The GEPIA database was used to analyze the correlation between CALR/HMGB1 expression and the overall survival of breast · · 641 [[PAGE_INDEX=24 FILE=08b612ef-59ff-47e1-960e-f599d97bfff7.pdf]] 中国肿瘤生物治疗杂志, 2026, 33(6) cancer patients. In vivo experiments: A TNBC mouse model was established by subcutaneous injection of 4T1-Luc cells into the mammary fat pad of female BALB/c mice. The mice were divided into three groups: Control group, doxorubicin hydrochloride (Dox) group, and MMR group. According to the grouping, intravenous administration was performed once every two days for a total of three consecutive doses. Tumor volume changes were monitored using an in vivo imaging system. Body weight and organ indices were recorded for preliminary safety assessment of vaccine. Histopathological changes in tumors were observed by hematoxylin-eosin (H-E) staining. The expression of CALR and HMGB1 in tumor tissues was detected by immunohistochemistry and Western blotting. Flow cytometry was used to analyze T lymphocyte subsets in the spleen, as well as the proportions of dendritic cells and macrophages in tumor. Immunohistochemistry was performed to detect CD8 + T lymphocyte infiltration in tumor tissues. The levels of pro-inflammatory cytokines IL-6 and TNF-α in serum were measured by ELISA. Results: MMR showed weak inhibitory effect on the viability of 4T1 cells but inhibited MDA-MB-231 cells by 90.39% (P < 0.001). Compared with the Control group, the MMR group exhibited upregulated expression of ICD-related proteins CALR, ATP and HMGB1 in MDA-MB-231 cells (P < 0.001). GEPIA database analysis indicated that patients with high expression of CALR and HMGB1 had prolonged survival. In vivo experiments, MMR delayed tumor volume growth (P < 0.001) and extended mouse survival. Within 28 days, there was no significant difference in body weight between the MMR group and the Control group (P > 0.05). H-E staining showed enlarged necrotic areas and immune cell infiltration in tumor tissues from the MMR group compared with the Control group. MMR upregulated the expression levels of the ICD-related proteins CALR and HMGB1. In the MMR group, the proportions of splenic CD4 + T and CD8 + T lymphocytes, as well as tumor-infiltrating dendritic cells and M1-type macrophages, were increased (P < 0.05). CD8 + T lymphocyte infiltration into tumors was also increased (P < 0.001), and the level of the pro-inflammatory cytokines IL-6 and TNF-α was upregulated (P < 0.01). Conclusion: The tumor- suppressive effect of the MMR vaccine on TNBC may be associated with the induction of ICD in tumors, thereby activating anti-tumor immunity.
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