CD274 and neoplasm: Assessing tumor tissue biomarkers in clinical practice faces several key limitations: (i) the limited availability and accessibility of tumor biopsies, as current companion diagnostic assays rely on tissue samples; (ii) tumor heterogeneity, which can cause a significant variability in evaluating markers like PD-L1 expression, TMB, or MSI depending on the biopsy section analyzed; and (iii) the presence of additional molecular mechanisms influencing the response to ICIs that may not be captured through standard tissue-based assessments [236].