Chanjuan Shi

Overview:

Dr. Shi is a gastrointestinal (GI)/liver pathologist. Her particular areas of interest are GI and pancreatic neuroendocrine tumors and pancreatic pathology. Her research interests include 1)  Pathobiology of GI and pancreatic neuroendocrine tumors and 2) Identification of diagnostic, prognostic and therapeutic biomarkers for colorectal and pancreatic cancers


Positions:

Professor of Pathology

Pathology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1989

Zhejiang University (China)

Ph.D. 2002

Dalhousie University (Canada)

Publications:

Multidimensional Immunophenotyping of Intraductal Papillary Mucinous Neoplasms Reveals Novel T Cell and Macrophage Signature.

BACKGROUND: Intraductal papillary mucinous neoplasms (IPMN) are the only radiographically identifiable precursor to pancreatic adenocarcinoma, yet little is known about how these lesions progress to cancer. Inflammation has been associated with dysplastic progression; however, the cause and composition of this inflammation remains poorly characterized. We sought to comprehensively profile immune cell infiltration using parallel spatial transcriptomic and flow cytometric techniques. METHODS: Twelve patients with resected IPMN exhibiting both high-grade dysplasia (HGD) and low-grade dysplasia (LGD) were selected for spatial transcriptomics (NanoString GeoMx). Immune (CD45+), epithelial (PanCK+), and stromal (SMA+) compartments were analyzed separately using the GeoMx NGS Pipeline. An additional 11 patients resected for IPMN of varying degrees of dysplasia underwent immunophenotyping using flow cytometry (DURAClone IM). RESULTS: Spatial transcriptomics revealed that T cells represent the dominant immune cell within IPMN stroma, which was confirmed by flow cytometry (56%). Spatial profiling found that the T-cell infiltrate was significantly higher in regions of LGD compared with HGD (62% vs. 50%, p = 0.038). Macrophages were the only other immune cell type with > 10% abundance, yet conversely, were generally more abundant in regions of HGD compared to LGD (19% vs. 11%, p = 0.058). Correspondingly, immune cells within regions of HGD demonstrated transcriptional upregulation of genes associated with macrophage activity including secretion (CXCL1) and phagocytosis (C1QA, C1S, C4B). CONCLUSIONS: IPMN immune infiltrate is primarily composed of T cells and macrophages. Regions of HGD appear to be relatively deplete of T cells and show a trend toward macrophage enrichment compared with regions of LGD.
Authors
Eckhoff, AM; Fletcher, AA; Landa, K; Iyer, M; Nussbaum, DP; Shi, C; Nair, SK; Allen, PJ
MLA Citation
Eckhoff, Austin M., et al. “Multidimensional Immunophenotyping of Intraductal Papillary Mucinous Neoplasms Reveals Novel T Cell and Macrophage Signature.Ann Surg Oncol, 2022. Pubmed, doi:10.1245/s10434-022-12157-0.
URI
https://scholars.duke.edu/individual/pub1521716
PMID
35831529
Source
pubmed
Published In
Annals of Surgical Oncology
Published Date
DOI
10.1245/s10434-022-12157-0

Liver Mass: Thinking Out of the Box.

Authors
Karachaliou, GS; Shi, C; Abdelmalek, MF
MLA Citation
Karachaliou, Georgia Sofia, et al. “Liver Mass: Thinking Out of the Box.Gastroenterology, vol. 163, no. 1, July 2022, pp. e10–12. Pubmed, doi:10.1053/j.gastro.2021.12.283.
URI
https://scholars.duke.edu/individual/pub1505823
PMID
34995531
Source
pubmed
Published In
Gastroenterology
Volume
163
Published Date
Start Page
e10
End Page
e12
DOI
10.1053/j.gastro.2021.12.283

Peak density of immature nerve cells occurs with high-grade dysplasia in intraductal papillary mucinous neoplasms of the pancreas.

The development of neural structures within tumors is now considered vital for carcinogenesis. However, the time course of this development in human pre-invasive neoplasia has been incompletely described. Therefore, we performed a detailed analysis of nerves across the neoplastic spectrum in resected intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Histology and multiplexed immunochemistry demonstrated that nerve density increased from low-grade (LG) to high-grade dysplasia (HG) but did not further increase once invasive IPMN (INV IPMN) was present. Higher nerve density correlated with increasing expression of nerve growth factor (NGF) by the tumor cells. Intra-tumoral nerves were immature and lacked markers of sympathetic, parasympathetic, and sensory lineages. Here, we show for the first time the presence of neural precursor cells (NPCs) within the stroma of pancreatic tumors. The density of these doublecortin (DCX)-positive NPCs increased from LG to HG, but not from HG to INV IPMN. We conclude that peak neural density of tumors is reached in high-grade dysplasia (often termed carcinoma in situ) rather than after invasion. These findings suggest that nerve-tumor interactions are important in IPMN progression and may serve as the basis for future mechanistic studies and novel therapeutic modalities. © 2022 The Pathological Society of Great Britain and Ireland.
Authors
Trinh, VQ-H; Roland, JT; Wong, J; Revetta, F; Patel, K; Shi, C; DelGiorno, KE; Carter, BD; Tan, MCB
MLA Citation
Trinh, Vincent Quoc-Huy, et al. “Peak density of immature nerve cells occurs with high-grade dysplasia in intraductal papillary mucinous neoplasms of the pancreas.J Pathol, June 2022. Pubmed, doi:10.1002/path.5978.
URI
https://scholars.duke.edu/individual/pub1524080
PMID
35686747
Source
pubmed
Published In
J Pathol
Published Date
DOI
10.1002/path.5978

Spatial Transcriptome Profiling of Intraductal Papillary Mucinous Neoplasms Nominates Novel Cyst Fluid Biomarkers of High-grade Dysplasia

Authors
Iyer, MK; Shi, C; Eckhoff, A; Nussbaum, D; Fletcher, A; Allen, P
MLA Citation
Iyer, Matthew K., et al. “Spatial Transcriptome Profiling of Intraductal Papillary Mucinous Neoplasms Nominates Novel Cyst Fluid Biomarkers of High-grade Dysplasia.” Annals of Surgical Oncology, vol. 29, no. SUPPL 2, 2022, pp. 352–352.
URI
https://scholars.duke.edu/individual/pub1521715
Source
wos-lite
Published In
Annals of Surgical Oncology
Volume
29
Published Date
Start Page
352
End Page
352

Safety and Efficacy of Avelumab in Small Bowel Adenocarcinoma.

INTRODUCTION: Small bowel adenocarcinomas (SBAs) are rare and frequently treated like large intestinal adenocarcinomas. However, SBAs have a very different microenvironment and could respond differently to the same therapies. Our previous data suggested that SBAs might benefit from targeting the PD-1/PD-L1 axis based on PD-L1 staining in almost 50% of SBA tissue samples tested. Thus, we designed a phase 2 study to explore safety and efficacy of avelumab in SBA. PATIENTS AND METHODS: Patients with advanced or metastatic disease were enrolled; ampullary tumors were considered part of the duodenum and allowed. Prior PD-1/PD-L1 inhibition was not allowed. Avelumab (10 mg/kg) was given every 2 weeks, and imaging was performed every 8 weeks. Primary endpoint was response rate. RESULTS: Eight patients (n = 5, small intestine; n = 3, ampullary) were enrolled, with a majority (88%) being male and a median age of 61 years. Of 7 efficacy-evaluable patients, 2 (29%) experienced partial responses; stable disease occurred in 3 additional patients (71%). Median progression-free survival was 3.35 months. Most frequent, related toxicities were anemia, fatigue, and infusion-related reaction (25% each), mostly grade ≤2; grade 3 hypokalemia and hyponatremia occurred in one patient, and another reported grade 4 diabetic ketoacidosis. CONCLUSIONS: Despite the observed benefit, accrual was slower than expected and the study was closed early due to feasibility. A general clinic observation was that patients were receiving immunotherapy off-label as the availability of these agents increased. Off-label availability and disease rarity were likely drivers of insufficient accrual.
Authors
Cardin, DB; Gilbert, J; Whisenant, JG; Ayers, GD; Jalikis, F; Dahlman, KB; O'Neal, JF; Revetta, F; Shi, C; Berlin, J
MLA Citation
Cardin, Dana B., et al. “Safety and Efficacy of Avelumab in Small Bowel Adenocarcinoma.Clin Colorectal Cancer, Mar. 2022. Pubmed, doi:10.1016/j.clcc.2022.03.003.
URI
https://scholars.duke.edu/individual/pub1518393
PMID
35450836
Source
pubmed
Published In
Clinical Colorectal Cancer
Published Date
DOI
10.1016/j.clcc.2022.03.003