Fig. 1

Overview of approved and exploratory biomarkers for immune checkpoint inhibitors (ICIs) in cancer. Tumor and immune features can influence response to ICIs and serve as predictive biomarkers for response. FDA- and EMA-approved biomarkers for ICIs in cancer are indicated in blue, while exploratory biomarkers are indicated in red. MSI and a high TMB contribute to the expression of tumor neoantigens presented by MHC I molecules on tumor cells that can be recognized by the TCR on CD8⁺ T cells, leading to antitumor T cell activity. In gastrointestinal cancers, the expression of immunogenic neoantigens in tumors with high TMB is dependent on certain mutational signatures [41]. On the other hand, binding of PD-L1 on tumor cells to PD-1 on T cells leads to the suppression of T cell antitumor activity. Additionally, exhausted T cells may also express the exhaustion markers TIM-3 and LAG-3. In lung adenocarcinoma, TP53 mutations are correlated with higher TMB and neoantigen expression, while TP53 missense but not nonsense mutations are associated with increased PD-L1 expression [42]. Various GES have also been associated with response to ICIs. IDO contributes to T cell suppression and its expression was induced in resistant HCC after ICI therapy [43]. The presence of B cells and TLS have been associated with improved prognosis and response to ICIs in several cancers, including sarcomas. Within the blood, a higher baseline circulating NLR has also been found to correlate with poorer outcomes in patients receiving ICIs in lung cancer [44].