RESUMO
OBJECTIVE: To investigate the effect of PD-1 monoclonal antibodies in tumor-associated macrophages on angiogenesis in cervical cancer and its mechanism of action. METHODS: The effect of PD-1 monoclonal antibodies on the progression of cervical cancer was assessed using the nude mouse xenograft model and HE staining; the impact of PD-1 monoclonal antibodies on cervical cancer cell migration was evaluated using wound healing assay and Transwell assay; the effect on vascular formation in cervical cancer cells was examined using an angiogenesis assay; the impact on the expression of related proteins was tested using Western blotting. RESULTS: PD-1 monoclonal antibodies in tumor-associated macrophages can regulate and thus inhibit the progression of cervical cancer while promoting the expression of SHP2. Additionally, Sindilizumab inhibited the expression of tissue-type fibrinogen activator K and HIF1α through the PD-1/IRE1α/SHP2 signaling pathway, which inhibited the migration and neovascularization of cervical cancer cells. CONCLUSIONS: This study discovered that PD-1 monoclonal antibodies in tumor-associated macrophages inhibit vascular generation inside cervical cancer by affecting the PD-1/IRE1α/SHP2/HIF1α signaling pathway, providing a new therapeutic target for the treatment of cervical cancer.
Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia , Camundongos Nus , Neovascularização Patológica , Receptor de Morte Celular Programada 1 , Transdução de Sinais , Macrófagos Associados a Tumor , Neoplasias do Colo do Útero , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/imunologia , Animais , Feminino , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor de Morte Celular Programada 1/metabolismo , Camundongos , Humanos , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/efeitos dos fármacos , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo , Movimento Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Background: The five-year recurrence rate of hepatocellular carcinoma (HCC) remains as high as 70%. A complete clinical response has not been observed without surgical resection. Here, we report a rare case of clinical complete response and long-term survival in a patient with massive HCC receiving treatment with immunotherapy, anti-angiogenic therapy, and radiotherapy. Case description: A 38-year-old woman presented to our hospital for abdominal pain that persisted for 3 months. She was diagnosed as Barcelona Clinic Liver Cancer(BCLC) stage A, with a Cancer of the Liver Italian Program (CLIP) score of 3, American Joint Committee on Cancer (AJCC) Tumor-Node-Metastasis (TNM) staging systems stage IB. She refused surgical resection and trans-arterial chemoembolization and accepted a non-invasive systematic treatment strategy involving immunotherapy, anti-angiogenic therapy, and radiotherapy. Her tumor burden decreased, and she experienced partial response before radiotherapy. Following radiotherapy, she experienced a complete clinical response and has been alive for more than 36 months after her initial presentation. She is currently alive. Conclusion: A non-invasive systematic treatment strategy is a potential radical treatment option for patients with massive HCC.