2025年 · 第03卷第06期

The human oral cavity harbors a diverse and dynamic microbial ecosystem, including bacteriophages (phages), which play a critical role in shaping the microbial community structure. Bacteriophages, viruses that specifically target and infect bacteria, have been increasingly recognized for their potential to influence both microbial balance and disease progression within the oral environment. Recent studies suggest that bacteriophages not only modulate the composition of the oral microbiome but also play an essential role in the pathogenesis and treatment of oral cancer. This review aims to explore the complex crosstalk between bacteriophages and oral health related to oral carcinogenesis, with a particular focus on their emerging roles in oral carcinogenesis and therapeutic interventions. Oral cancer, a major global health concern, is often associated with microbial dysbiosis and chronic inflammation, both of which contribute to tumor progression. Fusobacterium nucleatum, a key bacterial species implicated in oral carcinogenesis, has been shown to promote tumor growth, enhance immune evasion, and exacerbate inflammation within the tumor microenvironment. Bacteriophages offer a promising strategy to selectively target and eliminate such pathogenic bacteria such as Fusobacterium nucleatum, thereby restoring microbial balance and reducing the pro-tumorigenic effects of bacterial infections. Through the disruption of tumor-associated biofilms and modulation of cancer-promoting bacterial populations, phages may help mitigate the inflammatory responses that drive oral cancer progression. Additionally, phage therapy could complement existing treatments by sensitizing cancer cells to chemotherapy and immunotherapy. Beyond their direct antibacterial effects, genetically engineered bacteriophages present novel opportunities for targeted cancer therapy. Advances in synthetic biology have enabled the development of phages capable of delivering therapeutic payloads, such as anti-cancer peptides, cytotoxic agents, and immune modulators. These engineered phages can be designed to selectively target bacterial species that influence tumor progression, offering a highly specific and precision-based approach to oncology. Moreover, phages can serve as vectors for cancer vaccines, facilitating antigen presentation and enhancing immune responses against tumor cells. In addition to therapeutic applications, bacteriophages hold promise in the field of cancer diagnostics. The ability of phages to selectively bind to specific bacterial biomarkers associated with oral cancer could be leveraged for early disease detection and non-invasive screening. Phage-based biosensors, for instance, have shown potential in identifying cancer-associated microbial signatures, paving the way for innovative diagnostic tools that could improve early intervention and patient outcomes. Despite their potential, several challenges must be addressed before phage-based strategies can be fully integrated into clinical practice. Phage resistance, immune system clearance, and regulatory barriers pose significant hurdles to the widespread adoption of phage therapy. Additionally, the complex interactions between bacteriophages, host immunity, and the tumor microenvironment require further investigation to optimize therapeutic efficacy and safety. Advancing research on bacteriophages in the context of oral cancer could revolutionize current treatment paradigms, providing more targeted, efficient, and patient-friendly alternatives to conventional therapies. By harnessing the natural specificity and adaptability of bacteriophages, clinicians and researchers can develop innovative approaches to combat oral cancer, ultimately improving patient care and clinical outcomes.

Lung cancer is among the leading causes of cancer-related deaths worldwide, with treatment strategies primarily including surgery, chemotherapy, radiotherapy, and immunotherapy. Although immunotherapies targeting T cells and natural killer (NK) cells are widely used, therapies targeting neutrophils remain underdeveloped. Neutrophils are regarded as a specialized cell population that, once matured, lack the capacity for proliferation and are rapidly depleted in circulation, limiting their role to immune defense. However, recent discoveries have revealed that neutrophils represent a highly heterogeneous immune cell population, across diverse microenvironments. They are referred to as tumor-associated neutrophils when recruited to the tumor microenvironment. Initially, tumor-associated neutrophils were believed to primarily promote tumor growth and metastasis. Contrarily, emerging evidence indicates that tumor-associated neutrophils exhibit anti-tumor functions under specific conditions, acting as inhibitors during the initial growth or metastatic phases of lung cancer. This functional heterogeneity positions neutrophils as a promising focus for novel approaches to lung cancer immunotherapy. This review aims to explore the role of tumor-associated neutrophils in lung cancer progression and to investigate responses in the context of tumor control, thereby deepening the understanding of neutrophil function in lung cancer.

Antibiotic resistance and the growing burden of bacteria-induced cancers highlight the urgent need for innovative therapeutic approaches. Drug repurposing, leveraging pre-approved antibiotics for novel applications, is a promising strategy to address this challenge. Antibiotics designed to combat bacterial infections can inhibit microbial activity and target cellular mechanisms associated with oncogenesis. Chronic bacterial infections, such as those caused by Salmonella typhi, Helicobacter pylori, and Escherichia coli, contribute significantly to gallbladder, gastric, kidney, and bladder cancers. These infections induce inflammation, DNA damage, and the disruption of cellular pathways, promoting the development of cancer. Antibiotics such as doxycycline, rifampicin, and azithromycin demonstrate anticancer properties by inhibiting angiogenesis, inducing apoptosis, and regulating key pathways including the interleukin (IL)-6 signaling pathway and autophagy-related pathways. This dual action enhances chemotherapeutic efficacy and addresses bacteria-induced oncogenesis, offering a cost-effective and time-efficient alternative to traditional drug discovery. Herein, we review the intricate mechanisms by which bacteria-induced cancer arises and explore the groundbreaking potential of repurposing antibiotics as dual-action therapies in oncology. By elucidating the pivotal role of biofilms in persistent infections and highlighting untapped therapeutic opportunities in antibiotic repurposing, this review underscores a transformative approach to cancer treatment. This article explores the potential of repurposing antibiotic drugs for cancer treatment and highlights the prospects of drug repurposing strategies.

Lung cancer (LC) is one of the leading causes of cancer-related morbidity and mortality worldwide. Inflammation is a driver of cancer initiation and progression, affecting processes such as angiogenesis, antiapoptotic pathways, and DNA adduct formation. Cytokines are small proteins that can accelerate or slow tumor growth by controlling associated signaling processes such as cell proliferation, metastasis, and apoptosis. This review reveals the role of tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), transforming growth factor-beta (TGF-β), and interleukins in LC. Macrophages play a role in non-small cell lung cancer (NSCLC) pathogenesis and are associated with poor prognosis. A nested case-control study revealed that elevated concentrations of IL-6 and IL-8 were strongly associated with the risk of LC. Specifically, the odds ratio (OR) for IL-6 and IL-8 in former smokers (fourth quartile vs. first quartile) was 2.70 (95% confidence interval [CI], 1.55-4.70) and 2.83 (95% CI, 1.18-6.75), respectively. Because C-reactive protein levels are elevated in patients with NSCLC with larger and higher-grade tumors, CRP has been identified as a systemic indicator of chronic inflammation. Insulin-like growth factors influence cellular signal transduction pathways and contribute to tumorigenesis. Soluble tumor necrosis factor receptors have been explored for their role in NSCLC prognosis, highlighting their association with chromogranin. Transient receptor potential cation channel, subfamily M, member 7 (TRPM7), urokinase plasminogen activator, matrix metalloproteinases, and monocyte chemoattractant protein-1 have been identified with a focus on their expression patterns and prognostic significance in LC tissues. Moreover, lung angiogenesis induces vascular endothelial growth factor, soluble intercellular adhesion molecule-1, myeloperoxidase, and tissue inhibitors of metalloproteinase expressions. In conclusion, this review thoroughly summarized the inflammatory cytokines and specific factors influencing LC, providing the basis for further research on potential treatment approaches.

Background: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and the fourth most common cause of cancer-related mortality worldwide. Despite advances in immunotherapies and targeted treatments for HCC, chemotherapy remains a valuable first-line treatment. However, the efficacy of immunotherapy compared to that of chemotherapy is unknown. This study aimed to provide a comprehensive understanding of the effects of chemotherapy and immunotherapy on survival outcomes, response rates, and adverse effects. Methods: A thorough literature search of multiple electronic databases, including MEDLINE (PubMed), Embase, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov was conducted from each database’s inception to February 2024 to identify randomized controlled trials (RCTs) that compared first-line chemotherapy (doxorubicin, cisplatin, sorafenib, and fluorouracil) with immunotherapy (pembrolizumab nivolumab, and tislelizumab) for advanced HCC. Two reviewers independently identified the studies, obtained relevant information, and assessed the possibility of bias. The hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS) were merged using random effects meta-analysis. Results: Twenty studies with 1183 patients were examined. All studies had a high risk of bias. According to a meta-analysis, immunotherapy was linked to a significantly better PFS than chemotherapy (HR, 1.44, 95% confidence interval [CI], 1.04-2.00, I2 = 32%). OS showed a similar trend, although the difference was not statistically significant (HR, 1.26, 95% CI, 0.96-1.66, I2 = 0%). Sensitivity analysis revealed that immunotherapy continued to improve PFS compared to chemotherapy while having no discernible effect on OS. Conclusions: First-line immunotherapy may offer PFS advantages over chemotherapy for the treatment of advanced HCC. However, a high risk of bias limits definitive conclusions. Larger, higher-quality RCTs are needed to confirm the potential benefits of OS and minimize bias. Although chemotherapy remains a valuable option in resource-limited settings where access to targeted therapies is restricted, the widespread availability of immunotherapy makes it essential to compare both treatments to determine the most appropriate first-line option for advanced HCC.

Background: Several studies have demonstrated the synergistic effects of immunotherapy and radiotherapy for both local and abscopal tumor control. However, data regarding the use of first-line immunochemotherapy (ICT) combined with radiotherapy for advanced non-small cell lung cancer (NSCLC) remain limited. This study investigated the efficacy and safety of first-line immunochemotherapy combined with radiotherapy (ICRT) and those of ICT alone. Methods: Patients with advanced NSCLC who received first-line anti-programmed cell death protein 1 (PD-1) immunotherapy plus chemotherapy at Wuhan Union Hospital and Hunan Cancer Hospital between October 2017 and July 2021 were retrospectively analyzed. The objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety associated with treatment were assessed. Survival outcomes were analyzed using the Kaplan-Meier method. Results: A total of 194 patients were included: 92 were treated with ICRT and 102 were treated with ICT. The ORRs of the ICRT and ICT groups were 57.6% and 47.1%, respectively. Patients in the ICRT group had significantly longer PFS (median: 14.9 vs. 11.5 months; P = 0.035) and OS (median: 41.3 vs. 23.1 months; P = 0.047) than those of patients in the ICT group. Patients treated with thoracic radiotherapy, those treated with extrathoracic metastasis radiotherapy, and those treated without radiotherapy had median PFS of 21.5 months, 12.9 months, and 11.5 months (P = 0.031); and median OS was not reached, 41.3 months, and 23.1 months (P = 0.007), respectively. ICRT and ICT were generally well-tolerated, and the overall incidence of adverse events was similar between the groups. A total of 2.2% (2/92) of patients experienced grade 3 or grade 4 radiation-related adverse events. Conclusions: Radiotherapy is safe and manageable when added to first-line anti-PD-1 immunotherapy and chemotherapy for patients with advanced NSCLC.

Background: Synchronous oligometastatic esophageal squamous cell carcinoma (SOESCC), characterized by a limited number of metastases at diagnosis, represents a significant subset of esophageal squamous cell carcinoma. However, the optimal treatment modality for the condition has not been determined. Therefore, we aimed to evaluate the efficacy of local consolidative radiotherapy (cRT) for the primary tumor combined with first-line chemoimmunotherapy (CIT). Methods: This retrospective cohort study included 102 patients with SOESCC who underwent first-line CIT, either alone or in combination with cRT, between 2018 and 2022. We analyzed the progression-free survival (PFS) and overall survival (OS) in the two groups using propensity score matching (PSM). Univariate and multivariate Cox regression analyses were performed to identify prognostic factors associated with PFS and OS. Failure patterns were compared between groups. Results: Patients who received the additional cRT had longer PFS (median PFS, 11.5 vs. 8.3 months, P = 0.009) than did those who received CIT only; however, no significant difference was noted in OS (median OS, 20.0 vs. 17.0 months, P = 0.410) between the two groups. These results remained consistent after PSM and multivariate Cox regression analyses (PFS: hazard ratio [HR] 0.539, 95% confidence interval [CI], 0.312-0.932, P = 0.027; OS: HR, 0.580, 95% CI, 0.307-1.095, P = 0.093). Notably, the pattern of failure in the CIT group was primarily characterized by locoregional failure, in contrast to the distant failure observed in the CIT + cRT group. Locoregional failure-free survival in the CIT + cRT group was significantly lower than that in the CIT group (P < 0.001). Moreover, no statistically significant difference was observed in the incidence of treatment-related adverse events between the two groups. Conclusions: In patients with SOESCC, the combination of local cRT and first-line CIT prolonged PFS without increasing treatment-related toxicity. In addition, cRT for primary tumor significantly reduced the incidence of locoregional failure. This synergistic approach appears to be a viable and potentially superior treatment strategy for the treatment of SOESCC.