nCounter® PanCancer Immune Profiling Panel
A Multiplexed Gene Expression Approach To Profiling Cancer Immunology
The nCounter PanCancer Immune Profiling Panel is a novel new gene expression panel that enables researchers to develop profiles of the human immune response in all cancer types. In collaboration with cancer immunologists around the globe, our new 770 gene panel combines markers for 24 different immune cell types and populations, 30 common cancer antigens and genes that represent all categories of immune response including key checkpoint blockade genes.
- Explore Infiltrating Cell Types
- Understand Immune Pathway Activity
- Create Profiles of the Immune Response in Any Cancer Type
- 109 genes to cell surface markers for 24 different immune cell types and populations
- 30 genes for commonly studied CT Antigens
- Over 500 genes for measuring immune response
- 40 Reference Genes (including 30 overlapping controls with the PanCancer Pathways Panel)
- Customize with the addtion of up to 30 genes with our Panel-Plus feature
- Use Case 1
- Use Case 2
- Use Case 3
Selecting Adjuvants to Support Adoptive T Cell Therapy
Dr. Martin McIntosh, Fred Hutchinson Cancer Research Center
A growing number of cancer patients will be offered some type of adoptive T cell therapy, especially after conventional therapies fail3. Some patients have experienced dramatic improvements following T cell therapy, but many patients, even those whose tumors possess the target antigen, have not. Response rates could be improved by modulating the tumor microenvironment toward a state that is more supportive of immune function, and a number of existing tools can do this to some degree4,5; including cytokines, interleukins, interferons, checkpoint blockade (PD-1/PD-L1, BTLA-4, etc.), and others. Effective modulation strategies may require developing a molecular toolkit (assays and algorithms) that can accurately assess factors that are actionable and is practical for use in a clinical setting.
We plan to use the PanCancer Immune Profiling Panel to identify which actionable factors can be measured adequately using nucleic acid-based assays, with the goal to develop a parsimonious companion diagnostic for T cell therapies. This may be challenging for many reasons, including that solid tumors vary in ways that can confound appropriate interpretation, e.g. variations in both the cellular composition and in the expression level of specific cells in it. To start, we would profile tissues whose cellular composition and immune-environment has also been measured by gold-standard assays such as IHC, and also by clinically impractical flow cytometry, including tissues from patients who are enrolled in T cell therapy trials.
3 Pedrazzoli P, Comoli P, Montagna D, Demirer T, Bregni M. (2012) Is adoptive T-cell therapy for solid tumors coming of age? Bone Marrow Transplant 47:1013–1019.
4 Tey SK, Bollard CM, Heslop HE (2006) Adoptive T-cell transfer in cancer immunotherapy. Immunol Cell Biol 84:281–289.
5 Dougan M, Dranoff G. (2009) Immune therapy for cancer. Annu Rev Immunol 27:83–117.
Molecular Stratification of Laryngeal Cancer
Dr. Richard Young, Peter MacCallum Cancer Centre
There are no clinically useful prognostic or predictive molecular markers in laryngeal cancer, and despite recent advances in treatment, the five-year survival is less than 50%1. We have a large unique cohort of clinically annotated laryngeal cancer patients for whom we have formalin fixed paraffin embedded tumor tissue blocks. Our aim would be to use the PanCancer Immune Profiling Panel across samples from our cohort, given that immune modulating agents are showing preliminary efficacy in many cancers2.
We hope to be able to molecularly stratify patients based on expression profiles of immune-related genes and better identify molecules and pathways in the immune response that may have the potential to be therapeutically targeted. Ideally, these efforts will identify novel combinations of checkpoint inhibitors and other immunotherapeutic agents. The gene expression data from this panel has tremendous potential to allow us to more fully understand the interactions between the host immune system and tumor microenvironment and identify novel methods to predict and improve patient outcomes, with the ultimate aim of being able to provide molecular stratification tools of clinical utility in laryngeal cancer and potentially other head and neck cancers.
1 Corry J et al. (2011) Larynx preservation with primary non-surgical treatment for loco-regionally advanced larynx cancer. J Med Imaging Radiat Oncol 55:229–235.
2 Topalian SL et al. (2012) Safety, Activity, and Immune Correlates of Anti–PD-1 Antibody in Cancer. N Engl J Med 366:2443–2454.
Exploring Oncogenic Hepatitis C Virus-mediated Immune Dysregulation
Dr. Ravi Waldron, Stanford University
Chronic Hepatitis C Virus (HCV) infection is the leading cause of hepatocellular carcinoma (HCC) in the US and predisposes carriers to lymphoma and cholangiocarcinoma6-8. Although HCV is a small RNA virus and does not integrate directly into the host genome, it likely promotes tumorigenesis over time by attenuating anti-carcinogenic host immunity in order to evade the host immune system. Prior research has suggested that HCV induces PDCD-1 in peripheral blood mononuclear cells (PBMCs), decreasing host adaptive immunity by attenuating T cell and macrophage function9,10. Other literature also indicates that the innate immune system is modified by HCV in a way that promotes oncogenesis11. The host interferon response produced by PBMCs is attenuated by the virus via downregulation of STAT1 and upregulation of SOCS19,10. PBMC mediated IL17 pathways appear to be activated but ineffective at producing cytolysis12,13. In addition, TLR8 appears to be upregulated, but the pro-apoptotic effector molecules it signals, MyD88 and IRAK1, appear to downregulated by viral infection14. A full picture of the complex web of how HCV manipulates the immune system to promote both chronic infection and oncogenesis remains undescribed and may be invaluable to the early detection and chemotherapy of both HCC and HCV.
The new PanCancer Immune Profiling Panel provides a multiplex assay to comprehensively describe how virus induced modification of host immunity drives oncogenesis. This tool can assess gene expression in human PBMCs collected from HCV infected patients with HCC as compared to both HCV infected patients and uninfected patients. This will allow us to further elucidate the differential regulation of these pathways in the context of both HCC and HCV infection. We can then evaluate the hypothesis that oncogenic attenuation of host immunity occurs via virally induced dysregulation, which may indicate new biomarkers for early detection of tumor or drug targets for therapy.
6 Bosch FXX et al. (2004) Primary liver cancer: Worldwide incidence and trends. Gastroenterology 127:S5–S16.
7 Zignego AL, Giannini C, Gragnani L. (2012) HCV and lymphoproliferation. Clin Dev Immunol 2012.
8 El-Serag HB et al. (2009) Risk of hepatobiliary and pancreatic cancers after hepatitis C virus infection: A population-based study of U.S. veterans. Hepatology 49:116–123.
9 Frazier AD et al. (2010) Programmed death-1 affects suppressor of cytokine signaling-1 expression in T cells during hepatitis C infection. Viral Immunol 23:487–495.
10 Ma CJ et al. (2011) PD-1 negatively regulates interleukin-12 expression by limiting STAT-1 phosphorylation in monocytes/macrophages duringchronic hepatitis C virus infection. Immunology 132:421–431.
11 McGuinness PH, Painter D, Davies S, McCaughan GW. (2000) Increases in intrahepatic CD68 positive cells, MAC387 positive cells, and proinflammatory cytokines (particularly interleukin 18) in chronic hepatitis C infection. Gut 46:260–269.
12 Hao C et al. (2014) Imbalance of regulatory T cells and Th17 cells in patients with chronic hepatitis C. Immunology.
13 Kondo Y et al. (2014) HCV infection enhances Th17 commitment, which could affect the pathogenesis of autoimmune diseases. PLoS One 9.
14 Chen Y et al. (2013) HCV-Induced miR-21 Contributes to Evasion of Host Immune System by Targeting MyD88 and IRAK1. PLoS Pathog 9.