Molecular Analysis of the Immune Environment of Neuroendocrine Tumors and Associations with Clinical Outcomes
Researcher: Matthew H. Kulke, MD Location: Dana-Farber Cancer Institute State: Massachusetts Year: 2015 Status: Finished Grant Duration: 1 year
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To identify new ideas for treating neuroendocrine tumors based on knowledge about how they interact with the immune system.
Immune based therapies have demonstrated clear promise in the treatment of a number of human malignancies. In this project, Dr. Kulke and his team will evaluate a large cohort of neuroendocrine tumors to better understand how these tumors interact with the immune system, and to assess their potential to respond to immune therapies. This project could identify new ideas for treating neuroendocrine tumors based on knowledge about how they interact with the immune system.
Dr. Kulke’s findings will shed light on the potential for neuroendocrine tumors to respond to currently available immune checkpoint inhibitors, and inform future strategies for immunotherapy in neuroendocrine tumors.
To assess the expression of the key immune receptors PD-1 and PD-L1, in both tumor cells and associated stromal cells, in a large cohort of neuroendocrine tumors.
To characterize the tumor associated T-cell immune response, by measuring expression of the T cell markers CD3, CD8, CD45RO, and FOXP3 in tumor associated lymphocytes in the above cohort of tumor samples.
To assess associations between expression of PD-1, PD-L1, tumor associated lymphocytic response and the presence of CDKN1Bmutations (in small intestine neuroendocrine tumors) or mutations in MEN1, DAXX, or ATRX (in pancreatic neuroendocrine tumors).
To assess associations between expression of PD-1, PD-L1, tumor associated lymphocytic response, and clinical outcomes in the above cohort.
Immune checkpoint inhibition has emerged as a promising treatment approach in human malignancies. The potential for neuroendocrine tumors to respond to immune checkpoint inhibitors is unknown, and the immune environment of neuroendocrine tumors remains relatively unexplored. We propose to systematically evaluate the immune microenvironment of neuroendocrine tumors in a large and highly annotated biospecimen database that comprises a diverse set of neuroendocrine tumors. We will assess expression of key immune receptors in tumor and associated stromal cells. We will further assess whether these characteristics are associated with clinical outcomes.
NET Research Foundation
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