However, the clinical significance of PD-1(L)1 pathway upregulation in rectal cancers remains controversial and it is important to acknowledge that PD-L1 is an imperfect biomarker and that different analyses have highlighted how immunohistochemistry staining cut off differ among studies and how PD-L1 expression is not uniform, which could induce possible biased results related to sampling [35–38]. This evidence concerns the gene CD274 and rectal cancer.