Abstract 2797: Accumulation of neutrophils in the tumor microenvironment promotes resistance to immunotherapy in pancreatic cancer

Autor: Mark Choi, Jane Cullis, Despina Siolas, Dafna Bar-Sagi, Emily A. Vucic
Rok vydání: 2019
Předmět:
Zdroj: Cancer Research. 79:2797-2797
ISSN: 1538-7445
0008-5472
DOI: 10.1158/1538-7445.am2019-2797
Popis: The prognosis for pancreatic cancer patients is unequivocally poor. This is due in part to the fibrotic and immunosuppressive microenvironment of pancreatic tumors, which serves as a physical barrier to chemotherapy and immunotherapy. Intratumoral genetic alterations can cause remodeling of the immune environment through distinct cellular mechanisms. Oncogenic Kras gene mutations are the most frequently occurring genetic event in pancreatic cancer, followed by transforming alterations in TP53. We show that CRISPR/Cas engineered KrasG12D;Trp53R172H pancreatic ductal tumors have a distinct immune profile characterized by an increase in neutrophils and a concomitant decrease in cytotoxic and Th1+ T cells. In addition, KrasG12D;Trp53R172H pancreatic ductal tumors have an increase in CXCL5, a chemokine involved in neutrophil accumulation. Analysis of publicly available datasets shows that increased neutrophil numbers significantly correlate with decreased survival in pancreatic cancer patients. Of clinical relevance, p53-Crispr/Cas engineered pancreatic tumors in mice are resistant to immunotherapy/chemotherapy combination treatment. This data supports the possibility of personalizing immunotherapy treatments based on immune profiles. Citation Format: Despina Siolas, Emily Vucic, Jane Cullis, Mark Choi, Dafna Bar-Sagi. Accumulation of neutrophils in the tumor microenvironment promotes resistance to immunotherapy in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2797.
Databáze: OpenAIRE
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