Although the B2M mutation has been observed in pre-immunotherapy samples and was partly responsible for primary resistance mechanisms of anti-PD1/PDL1 therapy, more proofs exemplified that tumors including melanoma, CRC and lung cancer acquired B2M mutations in the course of the treatment and were resistant to PD1/PDL1 blockade consequently (acquired resistance) (Zaretsky et al., 2016; Gettinger et al., 2017; Sade-Feldman et al., 2017; Yeon Yeon et al., 2019). This evidence concerns the gene PDCD1 and melanoma.