Despite the common expression of checkpoint molecules such as PD-L1 on MDSC or CTLA-4 on Treg, it has been observed that anti-PD-L1 and anti-CTLA-4 treatments could only restore an efficient anti-tumor immune response in about 10% of metastatic tumor cases entirely, thus leading to a clinical complete response [252,253,254,255,256]. Here, CTLA4 is linked to metastatic neoplasm.