However, PD-1 pathway blockade has so far been unsuccessful in the treatment of a small number of patients with advanced PDA.[24] One plausible explanation for this lack of response in PDA patients is that the tumor infiltrating T cells may require blockade of additional immune checkpoints such as T cell immunoglobulin mucin 3 (Tim-3), LAG-3 or CTLA4 to restore anti-tumor function.[38] Alternatively, liver metastases – the most common cause of mortality in PDA – may be comprised of an entirely different immune microenvironment influenced by the uniquely tolerogenic milieu of the liver. This evidence concerns the gene HAVCR2 and neoplasm.