While the antigen burden (i.e., tumor mutation burden) is already considered a possible explanation for the tumor-size effect, our study suggests that even in spite of the pretreatment adaptation of tumor–immune populations, the marker of tumor size remains a limiting factor for the patient response to anti-PD-1 and anti-PD-L-1 treatments [50,51,52]. This evidence concerns the gene PDCD1 and neoplasm.