[Digitalization and multiplex IHC as predictive biomarkers for novel immune-therapeutics : New challenges for...

Molecular biology assays, for example next-generation sequencing, whole-exosome sequencing, and RNAseq, are well-established tools in precision oncology. Novel therapeutic concepts like bi- or multivalent antibodies may require different diagnostic approaches. In this context, multiplexed immunohistochemistry (IHC) in combination with digital image analysis offers a wide range of application possibilities.Many therapeutics currently tested in early clinical phases or preclinical development aim at the modulation of the immune response to the tumor. The respective diagnostic procedures have to address questions, e.g. regarding the spatial relationship of target and effector cells or the presence and ratio of certain cell subpopulations. These questions are also increasingly raised by the more classical therapeutics, such as monoclonal antibodies or antibody-drug conjugates.While it is hard to identify the same or adjacent cells in serial sections, multiplexed IHC assays combine oligoparametric analysis and cellular context. Establishment and validation of such assays is more complex than for common single-plex procedures with regard to specificity, accuracy and precision. Digital image analysis algorithms as an emerging tool for standardized evaluation of (multiplexed) IHC assays need to be set up in parallel with the wet lab procedures.This article focusses on the potential new role for multiplexed in situ assays in a yet-to-be-established precision pathology as a discipline of precision oncology.