VSIR and neoplasm: To permit more patients to benefit from immunotherapy, the focus has changed to targeting alternative novel immune checkpoints in the tumor microenvironment such as lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin, mucin domain 3 (TIM-3), T cell immunoglobulin, ITIM domain (TIGIT), V-domain immunoglobulin-containing suppressor of T cell activation (VISTA) and human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) forming the basis of next-generation ICIT [19] as shown in Figure 1.