This review discusses current literature on the production, function, and expression of nine soluble immune checkpoints – sPD-L1, sPD-1, sCTLA4, sCD80, sTIM3, sLAG3, sB7-H3, sBTLA, and sHVEM – in patients with solid tumors, and explores their role as biomarkers of response to ICI as well as to conventional therapies (chemotherapy, radiotherapy, targeted therapy, and surgery) in cancer patients. This evidence concerns the gene SPDL1 and cancer.