Critical immune suppressive pathways beyond PD-1/PD-L1 require greater attention. Nectins and nectin-like molecules might be promising targets for immunotherapy since they play critical roles in cell proliferation and migration and exert immunomodulatory functions in pathophysiological conditions. Here, we demonstrate that CD155 expression exceeds PD-L1 levels in tumors, and, is co-expressed with PD-L1 in both malignant cells and tumor-infiltrating myeloid cells. Using Cd155^-/- mice and CD155-deleted tumor cells we demonstrated distinct roles for host and tumor intrinsic CD155 in control of tumor development. Cd155^-/- mice displayed reduced tumor growth and metastasis via DNAM-1 upregulation and enhanced effector function of CD8⁺ T and NK cells, respectively. CD155-deleted tumor cells also displayed lower tumor growth and metastases demonstrating importance of a tumor intrinsic role of CD155. CD155 absence on host and tumor cells exerted an even greater inhibition of tumor growth and metastasis. Blockade of PD-1 or PD-1 and CTLA4 was more effective in settings in which CD155 was limiting, suggesting the clinical potential of co-targeting PD-L1 and CD155 function.  Our data suggest that reducing CD155 function on host and/or tumor cells may be potential alternative and collaborative strategies for tumor control. The anti-tumor efficacy of PD1 and/or CTLA4 blockade and CD155 inhibition are non-redundant and this finding could be therapeutically exploited for greater anti-tumor efficacy in treating cancer patients.