While understanding the reasons why certain patients are resistant to oncology therapies is important, it is even more critical to ensure that they are administered only to patients who are expected to respond. Therefore, the identification and use molecular markers that are predictive of response is imperative in bringing the curative potential of immuno-oncology drugs to more patients.

Neoantigen Load/Tumor Mutational Burden (TMB)
Despite the initial excitement surrounding the predictive potential of TMB as a biomarker of response, recent setbacks have called into question whether a simple count of non-synonymous somatic mutations is biologically informative enough to help guide treatment decisions. At Personalis, we believe that determining which of these mutations will be expressed as neoantigens and presented for immunosurveillance may be more indicative of a tumor’s potential susceptibility to immunotherapy.
Microsatellite Instability (MSI) Status
In 2017, MSI status became the first biomarker to be used in the FDA-approval of a cancer drug (Keytruda) for the treatment of advanced solid tumors based on a patient’s tumor biomarker status, rather than on tumor histology. This approval enabled clinicians to administer the drug to MSI-H patients; highlighting the clinical utility of MSI status as a predictive biomarker of immunotherapy response.
Immune Repertoire Profiling
Immune repertoire analysis has emerged as a major exploratory biomarker in predicting the likelihood of response to ICIs. Specifically, evaluating the clonality of the T-cell receptor (TCR) repertoire and identifying the most highly-expanded clonotypes in tumor samples have shown particular promise in this endeavor. With ImmunoID NeXT, it is now possible to characterize the immune repertoire using a broad content platform, and without the use of a separate, targeted immunosequencing kit, for which additional sample would be required.
Gene Expression Signatures
The inherent complexity of the tumor-immune interplay in the TME makes predicting response to immuno-oncology drugs exceptionally difficult. This has led to the increasingly-common evaluation of biomarkers that go beyond single genes and towards the analysis of more complex, multi-gene signatures. ImmunoID NeXT enables the assessment of all tumor- and/or immune-related genes and can facilitate the development of novel RNA expression signatures that may more effectively stratify responders from non-responders.
Predictive Biomarkers of Response
CategoryImmunoID NeXT Solutions
Neoantigen Load/Tumor Mutational Burden (TMB)
  • Neoantigen load
  • TMB
  • Synonymous and non-synonymous SNV and indel reporting
Microsatellite Instability (MSI) Status
  • Five canonical loci from the Updated Bethesda Consensus Panel
  • Proportion of all exome-wide MS-related loci found to be unstable
Immune Repertoire
  • TCRα chain repertoire profiling
  • TCRβ chain repertoire profiling
  • Characterization of clonality and top clonotypes
Gene Expression Signatures
  • Gene expression profiling of tumor- and/or immune-related genes
  • Advanced analysis for potential signature identification
Cancer-related Mutations
(SNVs, indels, fusions, and CNAs)
  • Validated exome-wide somatic variant detection at allelic fractions as low as 5%
  • Targeted panel-grade sensitivity/specificity across 247 clinically-relevant cancer driver genes
  • Neoantigen detection across all ~20,000 genes