This site is intended for
U.S.
Healthcare Professionals only.
Inflamed Tumor Markers
Inflamed tumors show evidence of immune-cell infiltration and activation in the tumor microenvironment.1,2 Several Immuno-Oncology (I-O) biomarkers exist that are reflective of an inflamed tumor microenvironment:
PD-L1
Programmed death ligand 1 (PD-L1), a ligand for the immune checkpoint receptor called programmed death receptor-1
- PD-L1 is a ligand for the immune checkpoint receptor called programmed death receptor-1 (PD-1), which is expressed on the surface of cytotoxic T cells
1-3
- PD-L1 is expressed on several cell types, including tumor cells and immune cells
Research is ongoing to better understand the role of PD-L1 as an I-O biomarker, both alone and in combination with other I-O biomarkers.
- PD-L1 may be expressed on tumor and/or immune cells at any point along a continuum of expression from 0% to 100%3-6
- PD-L1 expression may vary by tumor type, histology, location, and line of therapy3,5,6,8,9
- The cutoff points for defining high PD-L1 expression differ among tumor types and lines of therapy, and thus the potential for PD-L1 to predict responders for I-O therapy response may also differ across tumors6,9
- Assessment of PD-L1 expression can include looking for expression on tumor cells, select immune cells, or a combination of both4
- PD-L1 expression is determined by IHC and can be detected on tumor and immune cells6
- As multiple IHC assays are available, many studies have compared their analytical performance9,10
PD-L1: Exploration as an I-O biomarker
Learn about the role of PD-L1 as an
TILs
Tumor infiltrating lymphocytes (TILs) are recruited into the tumor microenvironment and may correlate with inflammation, and include cytotoxic T cells and natural killer cells.
- TILs are immune cells that enter the tumor and its microenvironment to mediate an antitumor immune response
- Expression of key secreted factors in the tumor microenvironment, such as chemokines and proinflammatory cytokines, can recruit these immune cells to the tumor2
- Tumors can be characterized by the extent of immune-cell infiltration
- The level of TILs correlates with the degree of inflammation3,4
- The number, type, and activation state of TILs found within a tumor can be identified using techniques such as IHC and cell-sorting technology such as flow cytometry5
Establishing the role of TILs in the tumor microenvironment
Learn about our research into TILs as a potential I-O biomarker
Watch videoInflammation Gene Signatures
Inflammation gene signatures are a specific type of gene expression profile (GEP) and can be used to assess inflammation signatures of a tumor microenvironment. They vary across tumor types and may be a powerful diagnostic tool.
Click below to learn more about inflammation gene signatures as a potential predictive I-O biomarker.- Inflammation gene signatures, a specific type of gene expression profile (GEP), can be used to assess inflammation signatures of a tumor microenvironment1
- GEP measures the expression of mRNA across huge sets of genes2
- This can create a distinct molecular profile (or gene signature), providing a holistic view of cellular function2,3
- Reflecting the combined expression of certain genes involved in the process of inflammation, inflammation gene signatures may indicate the presence of immune cells in the tumor microenvironment1,3
- Inflammation gene signatures vary across tumor types and may be a powerful diagnostic tool3-6
- These gene signatures may be used as surrogates for immune activity in the tumor microenvironment4
- The interferon gamma (IFN-γ) gene plays a major role in the activation of the immune response7
- Inflammation gene signatures, such as IFN-y, can be used to assess the level of inflammation within the tumor microenvironment8
- To assess gene signatures, mRNA expression is used as an intermediary to determine the expression levels of multiple genes2
- NGS can be used to assess GEP via RNA-seq, and gene expression panels (see hypothetical example of gene expression profile below)9,10
Get I-O Resources
Order or download
educational tools for your
patients and practice
References–Inflamed tumor markers
1. Masucci GV, Cesano A, Hawtin R, et al. Validation of biomarkers to predict response to immunotherapy in cancer: Volume I —
References–PD-L1
1. Freeman GJ, Long AJ, Iwai Y, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000;192(7):1027-1034. 2. Latchman Y, Wood CR, Chernova T, et al. PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat Immunol. 2001;2(3):261-268. 3. Gatalica Z, Snyder C, Maney T, et al. Programmed cell death 1 (PD-1) and its ligand (PD-L1) in common cancers and their correlation with molecular cancer type. Cancer Epidemiol Biomarkers Prev. 2014;23(12):2965-2970. 4. Taube JM, Klein A, Brahmer JR, et al. Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti–PD-1 therapy. Clin Cancer Res.
References–TILs
1. Wein L, Savas P, Luen SJ, Virassamy B, Salgado R, Loi S. Clinical validity and utility of tumor-infiltrating lymphocytes in routine clinical practice for breast cancer patients: current and future directions. Front Oncol. 2017. doi:10.3389/fonc.2017.00156. 2. Melero I, Rouzaut A, Motz GT, Coukos G. T-cell and
References–Inflammation gene signatures
1. Torri A, Beretta O, Ranghetti A, et al. Gene expression profiles identify inflammatory signatures in dendritic cells. PLoS One. 2010. doi:10.1371/journal.pone.0009404. 2. Walker MS, Hughes TA. Messenger RNA expression profiling using DNA microarray technology: diagnostic tool, scientific analysis or