Background: Hepatocellular carcinoma is the sixth most diagnosed malignancy and the fourth most common cause of cancer-related mortality globally. Despite progress in the treatment of liver cancer, nonsurgical treatments remain unsatisfactory, and only 15% of early-stage cases are surgically operable. Radiotherapy (RT) is a non-surgical treatment option for liver cancer when other traditional treatment methods are ineffective. However, RT has certain limitations, including eliciting poor therapeutic effects in patients with advanced and recurrent tumors. Tumor-associated macrophages (TAMs) are major inflammatory cells in the tumor microenvironment that are key to tumor development, angiogenesis, invasion, and metastasis, and they play an essential role in RT responses. Methods: We used big data analysis to determine the potential of targeting CXCL6/CXCR2. We enrolled 50 patients with liver cancer who received RT at our hospital. Tumor tissue samples were examined for any relationship between CXCL6/CXCR2 activity and patient prognosis. Using a cell coculture system (Transwell), we cocultured Huh7 liver cancer cells and THP-1 monocytes with and without CXCL6/CXCR2 small interfering RNA for 72 h. Results: The overexpression of CXCL6/CXCR2 was highly correlated with mortality. Our tissue study indicated a positive correlation between CXCL6/CXCR2 and M2-TAMs subsets. The coculture study demonstrated that THP-1 monocytes can secrete CXCL6, which acts on the CXCR2 receptor on the surface of Huh7 cells and activates IFN-g/p38 MAPK/NF-κB signals to promote the epithelial–mesenchymal transition and radio-resistance. Conclusions: Modulating the TAM/CXCL6/CXCR2 tumor immune signaling axis may be a new treatment strategy for the effective eradication of radiotherapy-resistant hepatocellular carcinoma cells.

Severe infection poses a major threat to cancer patients due to treatment-related immunosuppression. Early identification and timely intervention are essential to reducing infection-related mortality. This study investigated whether daily vital signs recorded during radiotherapy could predict severe infection. We conducted a retrospective case-control study of cancer patients who received radiotherapy between 2016 and 2022. Cases were patients who developed severe infection during radiotherapy, while controls completed radiotherapy without infection. Patients with over a 2-day interval between the last radiotherapy session and infection diagnosis were excluded. Included patients had ≥ 5 recorded daily vital-sign measurements. Collected data included demographics, vital signs, cancer type, treatments, comorbidities, and infection outcomes. Logistic regression and area under the receiver operating characteristic curve (AUROC) were used to assess predictive value. A total of 35 patients with severe infection and 200 controls were analyzed. Head and neck cancer and lung cancer were the most common cancer types in the infection group. Significant predictors included lower last systolic blood pressure (SBP), higher last heart rate (HR), an increased last shock index (SI, calculated as HR/SBP), and greater HR variability across the last 2 to 5 radiotherapy sessions. In multivariable models, last SI and HR variability remained independent predictors, with AUROC values ranging from 0.773 to 0.803. In cancer patients receiving radiotherapy, changes in HR, SBP, SI, and HR variability in the days preceding severe infection may serve as feasible, self-monitored indicators for early detection in outpatient or home settings. However, the relatively small number of infection events (n = 35) may limit the statistical robustness of our findings, and further validation is needed.