Li et al. profiled CD155 mRNA expression across 19 cancers and found that CD155 was upregulated in tumor cells and in tumor-infiltrating myeloid cells. Engineered genetic loss of CD155 in the host led to upregulation of costimulatory DNAM-1 (a receptor to CD155) on CD8+ T cells and NK cells, enhancing their function; CD8+ T cells reduced tumor growth while NK cells reduced metastasis. Loss of CD155 in the tumor reduced migration and survival, revealing non-redundant, tumor cell-intrinsic properties of CD155. Loss of CD155 further improved the antitumor efficacy of checkpoint blockades.
Critical immune-suppressive pathways beyond programmed death 1 (PD-1) and programmed death ligand 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 show CD155 expression in both malignant cells and tumor-infiltrating myeloid cells in humans and mice. 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 slower tumor growth and reduced metastases, demonstrating the 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 both PD-1 and CTLA4 was more effective in settings in which CD155 was limiting, suggesting the clinical potential of cotargeting PD-L1 and CD155 function.
Author Info: (1) Immunology in Cancer and Infection Laboratory and. (2) Immunology in Cancer and Infection Laboratory and. (3) Immunology in Cancer and Infection Laboratory and. (4) Medical Gen
Author Info: (1) Immunology in Cancer and Infection Laboratory and. (2) Immunology in Cancer and Infection Laboratory and. (3) Immunology in Cancer and Infection Laboratory and. (4) Medical Genomics, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia. (5) Immunology in Cancer and Infection Laboratory and. (6) Immunology in Cancer and Infection Laboratory and. (7) Immunology in Cancer and Infection Laboratory and. (8) Immunology in Cancer and Infection Laboratory and. (9) Immunology in Cancer and Infection Laboratory and. (10) Division of Cell Biology, Biomedical Research Center and Department of Biofunctional Microbiota, Graduate School of Medicine, Juntendo University, Tokyo, Japan. (11) Immunology in Cancer and Infection Laboratory and. (12) Immunology in Cancer and Infection Laboratory and. (13) Gordon and Jessie Gilmour Leukaemia Research Laboratory, Immunology Department, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. (14) Gordon and Jessie Gilmour Leukaemia Research Laboratory, Immunology Department, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. The Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia. School of Medicine, The University of Queensland, Herston, Queensland, Australia. (15) School of Medicine, The University of Queensland, Herston, Queensland, Australia. Cancer Immunoregulation and Immunotherapy and. (16) Immunology in Cancer and Infection Laboratory and. Immuno-oncology Discovery, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia. (17) Immunology in Cancer and Infection Laboratory and. School of Medicine, The University of Queensland, Herston, Queensland, Australia.
