Background: High mobility group protein B3 (HMGB3) is abundantly expressed in a number of malignancies, contributing to tumor cell growth and predicting poor outcomes. More research on the connection between HMGB3 and breast cancer is needed. The prognostic significance of HMGB3 in breast cancer was examined and validated in this study.Methods: Using The Cancer Genome Atlas (TCGA) database RNA sequencing and clinical data, we investigated the associations between HMGB3 expression and tumor mutations, prognosis, and immune infiltration in breast cancer. The Gene Expression Profiling Interactive Analysis (GEPIA), Tumor Immune Estimation Resource (TIMER), breast cancer gene-expression miner (bc-GenExMiner), UALCAN, OncoLnc, cBio Cancer Genomics Portal (cBioPortal), and LinkedOmics databases were applied to examine the levels of expression, mutation, coexpression, and immune correlation of HMGB3 in breast cancer. cBioPortal and the Database for Annotation, Visualization, and Integrated Discovery (DAVID) were used for coexpression and enrichment analyses, respectively. Experimental tests and a separate cohort of breast cancer patients in our center were used for validation. To determine independent risk factors affecting breast carcinoma prognosis, multivariate Cox regression analysis was performed. The Kaplan-Meier method was applied to analyze the connection between HMGB3 expression and overall survival time in breast cancer.Results: Pan-cancer investigation using the GEPIA and UALCAN databases revealed a high level of HMGB3 expression in different malignancies, including breast cancer. HMGB3 might be a potential diagnostic biomarker, according to the receiver operating characteristic (ROC) curve (AUC=0.932). And immunohistochemistry confirmed higher HMGB3 protein expression in breast cancer tissues in clinical samples. Experimental tests also showed that breast cancer cells have higher expression of HMGB3, and knockdown of HMGB3 can promote the proliferation of breast cancer cells and increase sensitivity to chemotherapy. Human epidermal growth factor receptor 2 (HER2), Nottingham Prognostic Index (NPI), basal-like status, nodal status (N+), triple-negative status, and Scarff-Bloom-Richardson (SBR) grade all showed positive correlations with HMGB3 expression. Conversely, HMGB3 expression was negatively associated with the expression of estrogen receptor (ER) and progesterone receptor (PR) in breast cancer. Breast cancer patients with high HMGB3 expression had poor overall survival, which was validated by an analysis of a separate cohort of breast cancer patients in our center. Cox regression analysis identified high HMGB3 expression as an independently associated risk factor for breast carcinoma. The amount of immunological infiltration was substantially linked with the high expression of HMGB3. The chromosome centromeric region, ATPase activity, and the cell cycle are critical areas where HMGB3 is involved, according to enrichment analysis. Therefore, we suspected that HMGB3 might be a potential biomarker for detecting and treating breast carcinoma.Conclusion: Breast cancer tissues had higher HMGB3 expression than normal breast tissues. HMGB3 overexpression may serve as an indicator for poor breast cancer outcomes.

Radioresistance of prostate cancer (PCa) is a major factor leading to local failure of radiotherapy. STAT3 is an oncogenic protein that was recently found to be activated in PCa tumors. This study aimed to investigate the radiosensitization effect of targeting STAT3 in PCa tumors. Here, the radiosensitization effect of STAT3 blockade was investigated by clonogenic assay, flow cytometry and western blot analysis in human PCa cells in vitro and in vivo. We demonstrated that STAT3 blockade with a STAT3 inhibitor or siRNA increased the radiosensitivity of PCa cells and that radiation together with STAT3 blockade induced more apoptosis and double-strand breaks (DSBs) than radiation alone in LNCaP cells. In addition, radiation induced STAT3 activation and survivin expression in PCa cells, which was inhibited by STAT3 blockade. Transfection with survivin cDNA attenuated the radiosensitization effect of STAT3 blockade. These effects were further confirmed by in vivo studies, which showed that the STAT3 inhibitor enhanced the treatment efficacy of radiation on LNCaP xenografts with decreased STAT3 activation and survivin expression. These findings suggest that STAT3 blockade radiosensitizes PCa cells through regulation of survivin. Thus, our study has revealed STAT3 as a potential sensitizer for irradiation in PCa cells. Its clinical application as an adjuvant in radiotherapy of PCa should be explored in the future.

Colorectal cancer has emerged as one of the predominant malignant tumors globally. Immunotherapy, as a novel therapeutic methodology, has opened up new possibilities for colorectal cancer patients. However, its actual clinical efficacy requires further enhancement. Copper, as an exceptionally crucial trace element, can influence various signaling pathways, gene expression, and biological metabolic processes in cells, thus playing a critical role in the pathogenesis of colorectal cancer. Recent studies have revealed that cuproptosis, a novel mode of cell death, holds promise to become a potential target to overcome resistance to colorectal cancer immunotherapy. This shows substantial potential in the combination treatment of colorectal cancer. Conveying copper into tumor cells via a nano-drug delivery system to induce cuproptosis of colorectal cancer cells could offer a potential strategy for eliminating drug-resistant colorectal cancer cells and vastly improving the efficacy of immunotherapy while ultimately destroy colorectal tumors. Moreover, combining the cuproptosis induction strategy with other anti-tumor approaches such as photothermal therapy, photodynamic therapy, and chemodynamic therapy could further enhance its therapeutic effect. This review aims to illuminate the practical significance of cuproptosis and cuproptosis-inducing nano-drugs in colorectal cancer immunotherapy, and scrutinize the current challenges and limitations of this methodology, thereby providing innovative thoughts and references for the advancement of cuproptosis-based colorectal cancer immunotherapy strategies.

Immunotherapy has become a significant research focus for cancer treatment in recent years because it can generate enduring immunological responses and has promising therapeutic potential. Nevertheless, excessive stimulation of the immune system may adversely affect healthy organs, which can lead to immune-related toxicities, including gastrointestinal, pulmonary, hepatic, and dermatological toxicities. Among them, gastrointestinal toxicity induced by the immune response is the most common. Immune-associated enteritis has an incidence rate of 8%-27% and is one of the most prevalent forms of gastrointestinal toxicity. Tislelizumab is an approved first-line treatment for individuals with recurrent or metastatic nasopharyngeal cancer functioning as an inhibitor of PD-1. Here, we report a patient with nasopharyngeal carcinoma who developed bloody stools and diarrhea after two cycles of tislelizumab. Abdominal CT revealed intestinal wall thickening with inflammatory exudation. Congestion, edema, and mucosal punctate ulcers were discovered during the colonoscopy. Histopathology confirmed active mucosal inflammation. The initial treatment with loperamide, bifidobacterium tetrad, and norfloxacin failed, but the symptoms improved significantly after switching to metronidazole, mesalazine, and methylprednisolone. This article reviewed a case of immunological enteritis triggered by tislelizumab, demonstrating that mesalazine can markedly alleviate the symptoms of immune-associated enteritis, aiming to enhance future clinical efforts regarding tislelizumab-induced immunological enteritis.

Objective This study aims to investigate the potential of Salvianic acid A (SAA) to enhance the efficacy of anti-PD-1 immunotherapy in triple-negative breast cancer (TNBC), with a focus on elucidating the mechanisms. Methods To explore the effects of SAA on anti-PD-1 therapy efficacy, we established a mouse tumor model using 4T1 breast cancer cells and treated groups with SAA, anti-PD-1 (αPD-1), or their combination. Tumor growth, weight, and survival were monitored. A melanoma mouse model using B16 melanoma cells was also used to validate the efficacy of SAA enhanced immunotherapy. Tumor tissues were analyzed histologically and by flow cytometry to assess immune cell infiltration and function. The expression of immune markers and cytokines was evaluated using immunohistochemistry, Western blot, and quantitative RT-PCR. In vitro experiments were conducted on 4T1, MDA-MB-231, and MDA-MB-453 breast cancer cell lines, as well as CD8 T cells and endothelial cells, to investigate the direct effects of SAA on cell viability, activation, and phenotype maintenance. Additionally, the impact of SAA on high endothelial venules (HEVs) was assessed using immunofluorescence and flow cytometry. Results The combination of SAA and anti-PD-1 therapy significantly inhibited tumor growth and prolonged survival in the 4T1 mouse model and B16 mouse model respectively, compared to controls (P < 0.001). Tumor volumes and weights were consistently lower in the combination group, with no significant weight loss or toxicity observed. Histological analysis revealed increased stromal content and reduced tumor cell density in the SAA + αPD-1 group, indicating enhanced immune cell infiltration and tumor cell death. Flow cytometry showed that SAA significantly increased the infiltration of CD8 T cells and stem-like CD8 T cells (TCF1 and SLAMF6) into the tumor microenvironment when combined with αPD-1 (P < 0.001). The combination also enhanced the expression of IFN-γ and Ki-67 in CD8 T cells, indicating improved functional capacity. Additionally, SAA promoted the formation of HEVs in tumor tissues, as evidenced by increased CD31 and MECA-79 staining (P < 0.001). In vitro, SAA did not directly inhibit breast cancer cell viability or activate CD8 T cells but maintained the high endothelial phenotype in endothelial cells by upregulating key markers such as ACKR1 and CDH5. These findings demonstrate that SAA enhances anti-PD-1 efficacy by modulating the tumor immune microenvironment and promoting HEV formation, without direct cytotoxic effects on cancer cells or immune cells. Conclusion SAA significantly enhances the efficacy of anti-PD-1 therapy by promoting HEV-mediated stem-like CD8 T cells infiltration in TNBC. The combination of SAA and αPD-1 represents a promising therapeutic strategy that warrants further exploration in preclinical and clinical settings.