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Generation of Orthotopic Pancreatic Tumors and Ex vivo Characterization of Tumor-Infiltrating T Cell Cytotoxicity
Published on: December 7, 2019
Multiomics Empowers Predictive Pancreatic Cancer Immunotherapy
Janelle M Montagne1,2,3, Elizabeth M Jaffee1,2,3, Elana J Fertig1,2
1Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.
Abstract:
Advances in cancer immunotherapy, particularly immune checkpoint inhibitors, have dramatically improved the prognosis for patients with metastatic melanoma and other previously incurable cancers. However, patients with pancreatic ductal adenocarcinoma (PDAC) generally do not respond to these therapies. PDAC is exceptionally difficult to treat because of its often late stage at diagnosis, modest mutation burden, and notoriously complex and immunosuppressive tumor microenvironment. Simultaneously interrogating features of cancer, immune, and other cellular components of the PDAC tumor microenvironment is therefore crucial for identifying biomarkers of immunotherapeutic resistance and response. Notably, single-cell and multiomics technologies, along with the analytical tools for interpreting corresponding data, are facilitating discoveries of the systems-level cellular and molecular interactions contributing to the overall resistance of PDAC to immunotherapy. Thus, in this review, we will explore how multiomics and single-cell analyses provide the unprecedented opportunity to identify biomarkers of resistance and response to successfully sensitize PDAC to immunotherapy.
Insights
Pancreatic cancer (PDAC) resists immunotherapy due to its complex tumor microenvironment. New multiomics and single-cell analyses can identify biomarkers to improve treatment responses.
Area of Science:
- Oncology and Immunology
- Cancer Research
- Translational Medicine
Background:
- Cancer immunotherapy, especially immune checkpoint inhibitors, has transformed outcomes for many advanced cancers.
- Pancreatic ductal adenocarcinoma (PDAC) patients typically exhibit poor responses to current immunotherapies.
- PDAC's resistance is attributed to late diagnosis, low mutation rates, and an immunosuppressive tumor microenvironment.
Approach:
- Interrogating the PDAC tumor microenvironment requires simultaneous analysis of cancer and immune cellular components.
- Single-cell and multiomics technologies offer powerful tools for dissecting complex cellular interactions.
- Advanced analytical methods are essential for interpreting the vast datasets generated by these technologies.
Key Points:
- Identifying biomarkers for immunotherapeutic resistance and response is critical for PDAC treatment.
- Multiomics and single-cell analyses enable systems-level understanding of PDAC's immune evasion mechanisms.
- These approaches facilitate the discovery of novel therapeutic targets and strategies.
Conclusions:
- Multiomics and single-cell analyses provide unprecedented opportunities to understand PDAC immunotherapy resistance.
- These advanced techniques can identify biomarkers to sensitize PDAC to immunotherapy.
- This research paves the way for developing more effective treatments for pancreatic cancer.
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