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Immune Landscape Signatures

Gene expression and analysis services for the detection of Immune Landscape Signatures attributable to 38 key immune cell subtypes, individual genes, and ratios

Interplay between various immune cell activities in human tumors contributes to patient responses to treatment with checkpoint inhibitors as well as overall patient outcomes. RNA expression analysis can be performed on Illumina RNA sequencing, NanoString or HTG EdgeSeq gene expression platforms using RNA or total nucleic acids isolated from FFPE or fresh frozen tumor specimens. Many immune signatures are also applicable to studies using PBMC or whole blood samples.

Results for the individual signatures are output as Immune Landscape Signature Scores, non-standardized and standardized across the project. The Immune Landscape Signature Scores can be used to determine immunogenic status of solid tumors. These signatures can also be used in a single- or multi-factor analysis of treatment response and survival, along with other clinicopathological and genomic co-factors such as tumor mutational burden.

Product Highlights

  • Detection of 38 Immune Landscape Signatures, characterizing key immune cell subtypes, pathways and individual genes, with potential predictive and prognostic utility across many cancer types (publication in progress).
  • Gene sets comprising individual Immune Landscape Signatures have been expertly developed across thousands of RNA expression tumor samples from various cancer indications to construct co-expression clusters attributed to specific immune cell subtypes.
  • All signatures show correlation with either event free survival (event, disease progression or death) or overall survival or both in multiple cancer types independent of the treatment type (publication in progress).
  • We offer streamlined analysis with flexibility to include novel genes or groups of genes of interest.
  • Available as an output from the following platforms:
    • Illumina RNA Access (preferred for FFPEs), Illumina TruSeq Stranded mRNA sequencing, Stranded Total Gold RNA sequencing
    • NanoString PanCancer Immune Profiling panel, NanoString PanCancer IO 360 panel
    • HTG EdgeSeq Immuno-Oncology panel, HTG EdgeSeq OBP panel

Immune Landscape Signatures
Signature Description
1 Cytotoxic Lymphocyte Immune Signature (CLIS) Anti-tumor immune activity including CD8+ cytotoxic T cells, natural killer cells, and CD4+ effector T cells
2 CD8+ T cell signature Primary adaptive immunity killer cells (cytotoxic T lymphocytes, or CTL)
3 B cell signature Antigen presentation and antibody production and generally associated with better outcomes
4 T cell Trafficking (TCT) signature CXCR3 Ligands, T cell recruitment
5  M2 TAM macrophage signature  Anti-inflammatory, tumor-promoting, and immune suppression activity
6 IFN-γ (IFNG) Key marker of general immune activity (single gene)
7 TGF-β  (TGFB1) Marker of general immunosuppressive activity (single gene)
8 Wound healing signature Promotes angiogenesis, may reflect chronic inflammation, and marker for immuno-suppressive activity, correlates with stemness
9 IFN-γ Response (IFNG response) signature Stromal response to IFN-γ (often suppressive)
10 TGF-β Response signature Stromal response to TGF-β (highly suppressive)
11 LAG3 Key marker of general immune activity (single gene)
12 FOXP3 Key marker of regulatory CD4+ T cells (single gene)
13 IFNG Interferon Gamma expression (single gene)
14 TGFB1 Key marker of immune suppression (single gene)
15 VSIR AKA VISTA, an immune checkpoint gene, inhibits T cell response (single gene)
16 Immature Dendritic Cell (iDC) signature Marker of general dendritic cell activity (generally associated with better outcomes)
17  IL anti-inflammatory signaling  Interleukin signaling associated with anti-inflammatory processes, primarily via IL5 and IL10
18  IL pro-inflammatory signaling  Interleukin signaling associated with pro-inflammatory processes, primarily via IL6 and IL8 and frequently an indicator of worse outcomes 
19  M0 macrophage signature  Biomarker of non-activated macrophage, associated with worse survival outcomes
20  M1 macrophage signature  Biomarker of polarized macrophage whose presence is generally anti-tumor
21  NK cell signature  Cytotoxic anti-tumor natural killer cell activity
22  NK CD56dim cell signature  A subtype of cytotoxic anti-tumor natural killer cells showing increased positive outcome association in certain tumor types
23  Th1 RAS GEF signature  Th1-specific aspects of the MEK/RAS pathway of extracellular signaling associated with guanine nucleotide exchange factors. High levels of this signature are overwhelming associated with worse outcomes.
24  Th2 IL signature  Indicator of interleukin Type 2 T helper cell activity
25  Th17 signature  Subset of pro-inflammatory T helper cells that originate separately from Th1 and Th2 lineages. They are sometimes positively and sometimes negatively associated with survival, depending on the indication.
26  T cell Trafficking / M2 TAM ratio  Recruitment vs. suppression of effector T cells. Useful outcome predictor in event-free and overall survival (Jones et al 2020 Cancers).
 aka TCT/M2TAM
27  CD28/CTLA4 ratio  T cell activation (CD28) / negative regulator (CTLA4) checkpoint
28  PD1/PDL1 ratio  T cell de-activation checkpoint.  Generally, high values of the PD1/PDL1 ratio imply better outcomes while low values of the ratio imply worse.
29   PD1 (PDCD1)  Important immune checkpoint gene (single gene)
30  PDL1 (CD274)  Important immune checkpoint gene (single gene)
31  CD28  Important immune checkpoint gene (single gene)
32  CTLA4  Important immune checkpoint gene (single gene)
33  NOS1  A mediator of anti-tumor activity. Its elevated presence in the TME, like TGFB1, is frequently associated with worse outcomes (single gene)
34  IRF8  A pleiotropic immune-related gene having mixed association depending on indication and outcome (single gene)
35  TOX  Supposedly a marker for T cell exhaustion but whose presence is often associated with better outcomes (single gene)
36  IL2  Cytokine important for T and B cell proliferation, and whose presence is more frequently associated with better outcomes (single gene)
37  IL6  Supports immunosuppressive MDSC and generally associated with worse outcomes (single gene)
38  IL10  A pleiotropic immune-related gene having mixed association depending on indication and outcome (single gene)

 

 

Product Deliverables

  • Immune Landscape Signature Score Card, standardized across project, per patient.
  • Platform-dependent raw data output files.
  • Custom statistical analysis for association with treatment response available.

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