Esophageal squamous cell carcinoma (ESCC), which is characterized by invasiveness and poor prognosis, is the sixth most common leading cause of cancer-related death worldwide. Despite advances in multimodality therapy, ESCC mortality remains high, and an understanding of the molecular changes that lead to ESCC development and progression remains limited. In the present study, Integrin Binding Sialoprotein (IBSP) upregulation was found in 182 of 269 (67.7%) primary ESCC cells at the mRNA level by quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, IHC staining further demonstrated that IBSP was upregulated in ESCC patients and IBSP protein upregulation was significantly related to the lymph node metastasis (P = 0.017), clinicopathologic stage (P = 0.001) and poor disease survival (P = 0.002). Moreover, functional studies illustrated that the IBSP gene can promote the proliferation and metastasis of ESCC cells. Furthermore, IBSP was found to regulate epithelial-mesenchymal transition (EMT), which promotes tumor cell metastasis. In conclusion, our study suggests that IBSP may be a valuable prognostic marker for ESCC patients.
Immunotherapy, as a novel treatment, has brought new hope to many patients with cancer, including patients with lung cancer. However, the overall cure rate and survival rate of lung cancer are still not satisfactory. The process of evolution has improved the ability of tumors to adapt to immunotherapy, which induces drug resistance. Many studies have focused on immunoresistance and achieved meaningful results. Therefore, it is necessary to have an in-depth understanding of the current research progress in immunoresistance, which will help to achieve good clinical results more efficiently.
Background PD-1/PD-L1 inhibitors in combination with chemotherapy are widely used in clinical practice. However, the ideal combined timing of them has not been fully explored. Methods In this study, simulation experiments to explore the impacts of the combination of anti-PD-1 antibody (anti-PD-1 Ab) on the cytotoxic effects of chemotherapeutic drugs in peripheral blood mononuclear cells were performed. In addition, the effects of the combined timing of PD-1/PD-L1 inhibitors and chemotherapy on efficacy and safety were retrospectively analysed in patients with refractory lung cancer. Results Experiments in vitro showed that administering the anti-PD-1 Ab 3 days after chemotherapy (represented by dicycloplatin) resulted in significantly weaker cytotoxic effects on lymphocytes, compared with administering the anti-PD-1 Ab before or concurrent with chemotherapy. Moreover, data from 64 lung cancer patients treated with PD-1/PD-L1 inhibitors plus chemotherapy as a second- or higher-line therapy were retrospectively analysed. The results showed that administering PD-1/PD-L1 inhibitors 1-10 days (especially 3-5 days) after chemotherapy was associated with longer overall survival [17.3 months versus 12.7 months; hazard ratio (HR) = 0.58, 95% confidence interval (CI) 0.28-1.19, P = 0.137 in univariate analysis; HR = 0.36, 95% CI 0.16-0.80, P = 0.012 in multivariate analysis] and a trend of improved progression-free survival (5.1 months versus 4.2 months; HR = 0.81, 95% CI 0.42-1.54, P = 0.512) compared with administering PD-1/PD-L1 inhibitors before or concurrent with chemotherapy. Conclusion Our findings suggest that administering PD-1/PD-L1 inhibitors 1-10 days (especially 3-5 days) after chemotherapy is superior to administering PD-1/PD-L1 inhibitors before or concurrent with chemotherapy in patients with refractory lung cancer, but this result needs to be further explored by prospective studies.
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