As researchers seek to harness the human immune system to fight cancer, they’re looking at several emerging opportunities to expand use of biomarkers. Among them:
- Human leukocyte antigen typing.
- Microbiome analysis for determining risk of inflammatory complications with immune therapeutics.
- Tumor mutation burden, measured via whole genome sequencing, whole exome sequencing, or comprehensive gene panel testing.
- T-cell receptor repertoire clonality, which is associated with response to PD-1 inhibition.
Meanwhile, a more traditional approach to using the body’s own defenses against cancer — blocking the interaction between the PD-1 protein and one of its ligands, PD-L1 — has shown impressive anti-tumor responses. Still, there remain many issues with using PD-L1 as a biomarker.
PD-L1 negativity is an unreliable indicator, as assays are technically difficult and imperfect. Results may differ depending on the antibody, assay, or tissue sample. And low expression, tumor heterogeneity, and inducible genes can lead to sampling errors and false negatives.
Consequently, we believe that PD-L1 may be more useful in identifying which tumors—rather than which patients — to treat. They also may be less relevant for combination therapies. To date, tumors that have appeared responsive to anti-PD-1 or anti-PD-L1 therapy include melanoma, renal cell carcinoma, non-small-cell lung cancer, bladder cancer, head and neck cancers, and lymphomas.
Other commonly used immunotherapy biomarkers include immunohistochemistry, flow cytometry, and next-generation sequencing — each presenting distinct pros and cons. For example:
- IHC is available in almost all local and central laboratories, is relatively inexpensive, and offers good availability of antibodies. On the minus side, data interpretation is subjective and throughput is limited.
- Flow cytometry provides robust detection of multiple markers within a cell population and is ideal for detecting and measuring several cell subsets. On the other hand, there is high assay variability, and panels are usually lab-specific.
- Next-generation sequencing offers high sensitivity to molecular changes and good reproducibility, while drawbacks include high cost and limited availability compared to competing technologies.
We took a detailed look at biomarkers and other current topics in a recent webinar, Expanding the Potential of Immuno-Oncology Therapies. Watch it now.