Immunotherapy has drastically improved the prognosis of many patients with cancer, but it can also lead to severe immune-related adverse events. Biomarkers, which are molecular markers that indicate a patient’s disease outcome or a patient’s response to treatment, are therefore crucial to helping clinicians weigh the potential benefits of immunotherapy against its potential toxicities. Immunohistochemistry (IHC) has thus far been a powerful technique for discovery and use of biomarkers such as CD8⁺ tumor-infiltrating lymphocytes. However, IHC has limited reproducibility. Thus, if more IHC-based biomarkers are to reach the clinic, refinement of the technique using multiplexing or automation is key.