GZMA and neoplasm: Other genes included in ICR signature are mainly involved in direct cytotoxic function, such as CD8, GNLY, GZMA, GZMB and GZMH. Finally, immunosuppressive mechanisms known as checkpoint inhibitors are considered in the signature and widely involved in ICI efficacy such as CD274, PDCD1 or CTLA4 but also IDO1 and FOXP3. IDO1 is involved in tryptophan metabolism and known to enhance the PI3K/AKT signaling and also with the T regulatory cell generation in tumor microenvironment, thus associated with poor prognosis in various tumor types [56, 57].