In vivo, these non-malignant cells contribute to the functional characteristics of CLL cells by interaction of their surface-bound ligands, including Cluster of Differentiation (CD) 40 (CD40) ligand, Programmed cell Death protein 1 (PD-1), Vascular Cell Adhesion Molecule 1 (VCAM-1), CD31, or soluble factors such as C-X-C motif chemokine ligand (CXCL) 12 (CXCL12) and CXCL13, Interleukin (IL) 6 (IL-6) and IL-10, B cell Activating Factor (BAFF) and A Proliferation-Inducing Ligand (APRIL), with cognate receptors on the plasma membrane of CLL cells themselves [13,14,15,16]. Here, PDCD1 is linked to B-cell chronic lymphocytic leukemia.