Alternative novel immune checkpoints in the tumor microenvironment have been detected as potential targets (e.g., T-cell immunoglobulin mucin-3 (TIM-3)/galectin-9, lymphocyte-activation gene 3 (LAG-3) or T cell immunoglobulin and ITIM domains (TIGIT)) in order to enhance the benefit from CI especially in patients with resistance to PD-1/PD-L1/CTLA-4 mAbs. This evidence concerns the gene HAVCR2 and neoplasm.