Toward a better pan-tumor predictive signature for unleashing precision immuno-oncology.

While immune checkpoint inhibition (ICI) has revolutionized therapy across solid tumors, resistance remains an issue. Programmed death ligand-1 immunohistochemistry has limited clinical utility, whereas tumor mutation burden and microsatellite instability are only valuable for a minority of patients and leave room for improvement. Multiomic gene signatures have enhanced prediction of immune response by incorporating interferon-gamma signaling, T-cell dysfunction and exhaustion genes, and myeloid signatures. Single-cell RNA technology has been adopted to further optimize prediction of response to immunotherapy. A novel Immune Profile Score is presented by Zander et al that builds on prior immune signatures, using DNA and RNA profiling to predict outcomes across solid tumors receiving ICIs. While this assay is promising, further prospective validation and refinements will be necessary to realize its full potential in our quest to develop precision immuno-oncology. The incorporation of readily available clinical factors (eg, sites of metastasis), host genetics, orthogonal molecular platforms (microbiome, computational pathology, spatial transcriptomics, epigenetics, proteomics, radiomics) and investigating biomarkers to predict primary refractory disease and severe toxicities may further facilitate precision medicine.