To this regard, in chemorefractory pMMR/MSS mCRC patients, Le et al. and Chen et al. showed a lack of efficacy of the anti-PD1 pembrolizumab and a modest clinical benefit of the anti-PD-L1 durvalumab plus the anti-CTLA-4 tremelimumab, reserved only to patients with a tumour mutational burden (TMB) more than 28 mut/Mb on circulating tumour DNA, respectively [4,20]. The gene discussed is PDCD1; the disease is neoplasm.