Background Triple-negative breast cancer (TNBC) is an aggressive cancer that affects about 13/100,000 women yearly. Patients with TNBC are often resistant to endocrine and molecular targeted therapy, making clinical treatment challenging. Researches indicate that tumor microenvironment (TME) is related to prognosis in many cancers. Therefore, we aim to identify TME immune-related biomarkers to enhance the prognosis and immunotherapy efficacy in patients with TNBC. Methods The bulk mRNA transcriptome data and clinical information of the (GSE58812) and (GSE25055) datasets were downloaded from the Gene Expression Omnibus (GEO) database, and the ESTIMATE algorithm was used to calculate the ImmuneScore, StromalScore, and ESTIMATEScore. Patients were divided into low and high groups according to the quartiles of ImmuneScore, StromalScore, and the median of ESTIMATEScore to filter differential expression genes (DEGs), respectively. The DEGs were then evaluated using univariate and multivariate Cox regression to identify TME-related genes and its association with survival rate for the construction of a TMErisk model with three biomarkers. Then Gene Expression Profiling Interactive Analysis (GEPIA) and The Cancer Genome Atlas (TCGA) data were used to compare the gene expression in cancer and normal tissues. xCell analysis calculated the proportion of tumor-infiltrating immune cells in low and high expression of ATPase Secretory Pathway Ca 2+ Transporting 2 ( ATP2C2 ). In addition, samples from 20 TNBC patients admitted to our institution were used for immunohistochemical (IHC) examination. Results Three immune-related DEGs were identified, including prolyl 3-hydroxylase 2 ( P3H2 ), sodium voltage-gated channel beta subunit 3 ( SCN3B ), and ATP2C2 and a TMErisk model was constructed and validated. However, only ATP2C2 was selected for further analysis. ATP2C2 mRNA level of TNBC patients was higher than that of normal breast tissue. Survival analysis showed that patients with high expression of ATP2C2 had a bad prognosis. xCell analysis demonstrated that the expression of ATP2C2 was associated with 16 kinds of tumor-infiltrating immune cells. Protein expression of ATP2C2 in TNBC tissues was higher compared to paired normal tissues in IHC. Conclusions This study constructed and validated a TMErisk model that can effectively predict 3- and 5-year survival rate for TNBC patients. TNBC patients with lower expression of ATP2C2 had a good prognosis.

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Stimulating immunogenic cell death (ICD) is the key to tumor immunotherapy. However, traditional chemoradiotherapy has limited effect on stimulating immunity and often requires repeated administration, which greatly reduces the tumor-killing effect. In this article, we created a sodium alginate hydrogel sustained-release system containing low-dose doxorubicin (Dox) and immune adjuvant R837, which were injected into the interstitial space to wrap around the tumor in situ, achieving a sustained release and long-lasting immune response. Cooperating with immune checkpoint blockade, Dox induced ICD, activated dendritic cells (DCs) and converted immunosuppressive M2-type tumor-associated macrophages (TAM) to tumor-killing M1-type TAMs. Simultaneously, it greatly promoted T cell proliferation and infiltration, and reduced tumor immunosuppressive factors, triggering a robust immune response to suppress tumors in vivo. In conclusion, this anti-tumor strategy based on interstitial injection can achieve continuous local immune stimulation by low-dose chemotherapy drugs, providing a potential approach for tumor immunotherapy.