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Intertumoral Lineage Diversity and Immunosuppressive Transcriptional Programs in Well-differentiated Gastroenteropancreatic Neuroendocrine Tumors by Samantha E. Hoffman; Todd W. Dowrey; Carlos Villacorta Martin; Kevin Bi; Breanna Titchen; Shreya Johri; Laura DelloStritto; Miraj Patel; Colin Mackichan; Stephanie Inga; Judy Chen; Grace Grimaldi; Sara Napolitano; Isaac Wakiro; Jingyi Wu; Jason Yeung; Asaf Rotem; Erin Shannon; Thomas Clancy; Jiping Wang; Sarah Denning; Lauren Brais; Ying Huang; Katrina Z. Kao; Scott Rodig; Jason L. Hornick; Sebastien Vigneau; Jihye Park; Matthew H. Kulke; Jennifer Chan; Eliezer M. Van Allen; George J. Murphy is a scholarly article available to read on EtoBox.

What is Intertumoral Lineage Diversity and Immunosuppressive Transcriptional Programs in Well-differentiated Gastroenteropancreatic Neuroendocrine Tumors about?

## ABSTRACT Neuroendocrine tumors (NETs) are rare cancers that may arise in the gastrointestinal tract and pancreas. The fundamental mechanisms driving gastroenteropancreatic (GEP) NET growth remain incompletely elucidated; however, the heterogeneous clinical behavior of GEP-NETs suggests that both cellular lineage dynamics and tumor microenvironment influence tumor pathophysiology. Here, we investigated the single-cell transcriptomes of tumor and immune cells from patients with gastroenteropancreatic NETs. Malignant GEP-NET cells expressed genes and regulons associated with normal, gastrointestinal endocrine cell differentiation and fate determination stages. While tumor and lymphoid compartments sparsely expressed immunosuppressive targets, infiltrating myeloid cells were enriched for alternative immunotherapy pathways includingVSIR, Tim3/Gal9, andSIGLEC10. Finally, analysis of paired primary and metastatic tissue specimens from small intestinal NETs demonstrated transcriptional transformation between the primary tumor and its distant metastasis. Our findings highlight the transcriptomic heterogeneity that distinguishes the cellular landscapes of GEP-NET anatomic subtypes and rev

Author

Samantha E. Hoffman; Todd W. Dowrey; Carlos Villacorta Martin; Kevin Bi; Breanna Titchen; Shreya Johri; Laura DelloStritto; Miraj Patel; Colin Mackichan; Stephanie Inga; Judy Chen; Grace Grimaldi; Sara Napolitano; Isaac Wakiro; Jingyi Wu; Jason Yeung; Asaf Rotem; Erin Shannon; Thomas Clancy; Jiping Wang; Sarah Denning; Lauren Brais; Ying Huang; Katrina Z. Kao; Scott Rodig; Jason L. Hornick; Sebastien Vigneau; Jihye Park; Matthew H. Kulke; Jennifer Chan; Eliezer M. Van Allen; George J. Murphy

Publisher

Cold Spring Harbor Laboratory

Published

2022

Language

EN