Distinctive grade based on Ki67 index and immune microenvironment of metastatic pancreatic neuroendocrine tumors responding to capecitabine plus temozolomide

• Published in: BMC cancer 2024-11, Vol.24 (1), p.1362-10, Article 1362
• Main Authors: Gao, Heli, Zhang, Wuhu, Li, Zheng, Liu, Wensheng, Liu, Mengqi, Zhuo, Qifeng, Shi, Yihua, Xu, Wenyan, Zhou, Chenjie, Qin, Yi, Xu, Jin, Chen, Jie, Yu, Xianjun, Xu, Xiaowu, Ji, Shunrong
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antimitotic agents; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biopsy; Capecitabine - administration & dosage; Capecitabine - therapeutic use; Capecitabine/temozolomide; Care and treatment; CD11b antigen; CD163 antigen; CD25 antigen; CD4 antigen; CD80 antigen; CD86 antigen; Chemotherapy; Development and progression; Diagnosis; Dosage and administration; Female; Humans; Immunofluorescence; Immunoregulation; Ki-67 Antigen - metabolism; Ki67 index; Liver; Lymphocytes T; Macrophages; Male; Medical prognosis; Metastases; Metastasis; Microenvironments; Middle Aged; Neoplasm Grading; Neuroendocrine tumors; Neuroendocrine Tumors - drug therapy; Neuroendocrine Tumors - immunology; Neuroendocrine Tumors - pathology; Pancreas; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - immunology; Pancreatic Neoplasms - pathology; Pancreatic neuroendocrine tumor; Pancreatic tumors; Patients; Retrospective Studies; Suppressor cells; Surgery; Temozolomide; Temozolomide - administration & dosage; Temozolomide - pharmacology; Temozolomide - therapeutic use; Testing; Treatment Outcome; Tumor antigens; Tumor microenvironment; Tumor Microenvironment - drug effects; Tumor Microenvironment - immunology; Upgrading; Variance analysis
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-024-13117-5

Ki67 index changes during the treatment of metastatic pancreatic neuroendocrine tumor (PanNET) treatment. The study aimed to detect alterations of grade based on Ki67 index and immune microenvironment in PanNET responding to capecitabine/temozolomide (CapTem). Retrospective data of patients with PanNET were collected. In control group, 35 patients underwent surgery immediately after biopsy. In CapTem group, 38 patients received CapTem after biopsy and responded well to treatment (defined as either stable disease or partial response), and subsequently underwent surgery. All patients have pathological Ki67 index at biopsy and after surgery. CD163 + CD68 + CD206 + M2 macrophages, CD68 + CD86 + CD80 + M1 macrophages, CD11b + CD33 + myeloid-derived suppressor cells, and CD4 + CD25 + regulatory T cells were stained using multiplex immunofluorescence. In control group, the paired grade based on Ki67 index directly after surgery showed no upgrade or downgrade compared to biopsy. In patients who responded well to CapTem, the grade based on Ki67 index before and after CapTem was altered. Thirteen patients had upgraded Ki67 index and 11 patients had downgraded. The proportion of stable disease was higher in the upgraded group compared to downgraded group (p = 0.0155). And upgraded group had a significantly shorter mPFS than patients in the downgrade group (8.5 months vs. 20 months, HR 4.834, 95% CI 1.414 to 16.53, p = 0.012). M1 macrophages was significantly lower in the downgraded group than in the Ki67 upgraded group (p