Abstract B032: Evaluating T cell-inflammation in pancreatic neuroendocrine tumors

Abstract Background: Pancreatic neuroendocrine tumors (pNETs) are rare tumors arising from neuroendocrine cells in the pancreas. Their clinical behaviour and prognosis are variable and durable responses are often difficult to achieve with conventional therapies. Immunotherapy approaches may be efficacious in a subgroup of pNETs. In a recent study that did not include pNETs, we showed that a four-chemokine signature (c-Score: CCL4, CCL5, CXCL9, CXCL10) predicts T cell-inflammation and response to immune checkpoint inhibitors across cancers. We have hypothesized that the c-Score will also identify pNET subgroups with T cell-inflammation. Methods: The c-Score and hallmarks of the cancer-immunity cycle are being evaluated in pNETs as a cohort study (n=100 cases) of the Marathon of Hope Cancer Centres Network whole genome and transcriptome tumor sequencing (WGTS) project. The cohort study will compare pNET profiles with those of other pancreatic and peri-ampullary tumors. Results: As of June 1, 2024, primary tumor data from 23 cases were available for analysis, including 16 pNETs, 2 pancreatic ductal adenocarcinomas (PDAC), 2 pancreatic adenosquamous carcinoma (PASC), 2 distal cholangiocarcinomas (dCCA), and 1 ampullary carcinoma (AC). Dimension reduction by principle component analysis (PCA) revealed clustering based on histological subtype. Interestingly, PCA using immune genes also demonstrate subgrouping that overlapped with the histological subtypes, suggesting that immunity of pancreatic/peri-ampullary neoplasms may be directed by histological types rather than the pancreas gland itself. These cancers showed a broad distribution of c-Score expression, with pNETs having the lowest c-Score. Tumors with high expression of the c-Score, including 2 pNETs, had increased expression of cancer-immunity cycle gene sets. DUX4, FAM186A, and IGFN1 were amongst the most common genes mutated in all tumors. Conclusions: Early data suggest that pNETs generally harbor low c-Score values and hallmarks of cancer-immunity, with the existence of a subgroup of pNETs displaying T cell-inflammation. Citation Format: Joan Miguel Romero, James Vafiadis, Tess Aalto, Ruomeng Fang, Yifan Wang, George Zogopoulos. Evaluating T cell-inflammation in pancreatic neuroendocrine tumors [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B032.