On March 18, 2022, the combination therapy of relatlimab and nivolumab was approved by FDA for the treatment of unresectable or metastatic melanoma, making LAG3 the third FDA-approved immune checkpoint that was approved by FDA after CTLA-4 and PD-1 axis.423,424 This approval of LAG3 mAb marks an exciting beginning for this inhibitory receptor but many aspects of its biological functions still remain enigmatic. This evidence concerns the gene CTLA4 and metastatic melanoma.