Table 2.
Summary of Included Predictive Biomarkers in ICI Therapy
| Biomarker | Validated | Platform | Tumor Type | Sample Source | Comments | References |
|---|---|---|---|---|---|---|
| PD-L1 Expression | Yes | IHC | Multiple Cancer Types | Tumor tissue | Subject to intratumor and temporal heterogeneity; Trials use varied cut-offs and determination methods (ie, TPS, CPS) | [20, 34–50] |
| MSI/MMR Status | Yes | PCR-based or IHC | Multiple Cancer Types | Tumor tissue | Approved for use as a tumor-agnostic biomarker | [49, 50, 72–74] |
| Tumor Mutational Burden | Yes (see comments) | NGS-based (WES or targeted gene panel) | Multiple Cancer Types | Blood or Tumor tissue | Two platforms – Foundation One CDx and MSK-IMPACT have received FDA approval; Available platforms use different cut-offs for defining “high TMB” | [58–61] |
| JAK ½ Mutation | No | NGS-based (WES or targeted gene panel) | Melanoma | Blood or Tumor tissue | Rare and subject to validation | [62] |
| β2-microglobulin | No | NGS-based (WES or targeted gene panel) | Melanoma | Blood or Tumor tissue | Rare and subject to validation | [63] |
| HLA Class I Diversity | No | NGS-based (WES or targeted gene panel) | Melanoma and NSCLC | Blood | Subject to validation | [56] |
| HLA Class I LOH | No | NGS-based | NSCLC | Tumor tissue | Subject to validation | [57] |
| TME Contexture | ||||||
| Immunoscore | Yes (see comments) | IHC | Colorectal Cancer | Tumor tissue | Validated in early-stage colorectal cancer only | [64,76,78] |
| Consensus Molecular Profile | No | Gene Expression Profiling | Colorectal Cancer | Tumor tissue | Subject to validation | [64,82] |
| Systemic Biomarkers | No | Varied | Multiple | Blood | Blood biomarkers (eg, NLR, PLR, LDH) serve as surrogates for determining systemic inflammation; cut-offs are varied and subject to validation | [83–88] |
| Gut Microbiome | No | PCR or NGS | Multiple | Gut | Subject to validation | [89,93] |
Abbreviations: IHC, immunohistochemistry; NGS, next generation sequencing; WES, whole exome sequencing; PCR, polymerase chain reaction; NSCLC, non small cell lung cancer; TPS, tumor proportion score; CPS, combined positive score; NLR, neutrophil to lymphocyte ratio; PLR, platelet to lymphocyte ration; LDH, lactate dehydrogenase.