Other combinations use a variety of mechanisms to manipulate the TME, such as combining PD-1 with PD-L1 antagonism to increase effector T cells [63], ICI with SEMA4D inhibition to enable leukocyte penetration into the tumor and reduce M2 tumor-associated macrophages and MDSC [36,64], ICI with CCR2/CCR5 inhibition to enable chemotaxis [30], and ICI with manipulation of the gut microbiome [65]. The gene discussed is PDCD1; the disease is neoplasm.