| First Author | Baghdadi M | Year | 2013 |
| Journal | Immunity | Volume | 39 |
| Issue | 6 | Pages | 1070-81 |
| PubMed ID | 24315994 | Mgi Jnum | J:209302 |
| Mgi Id | MGI:5566940 | Doi | 10.1016/j.immuni.2013.09.014 |
| Citation | Baghdadi M, et al. (2013) TIM-4 glycoprotein-mediated degradation of dying tumor cells by autophagy leads to reduced antigen presentation and increased immune tolerance. Immunity 39(6):1070-81 |
| abstractText | Phagocytosis of apoptotic cells by myeloid cells has been implicated in the maintenance of immune homeostasis. In this study, we found that T cell immunoglobulin- and mucin domain-containing molecule-4 (TIM-4) repressed tumor-specific immunity triggered by chemotherapy-induced tumor cell death. TIM-4 was found to be highly expressed on tumor-associated myeloid cells such as macrophages (TAMs) and dendritic cells (TADCs) and danger-associated molecular patterns (DAMPs) released from chemotherapy-damaged tumor cells induced TIM-4 on tumor-associated myeloid cells recruited from bone marrow-derived precursors. TIM-4 directly interacted with AMPKalpha1 and activated autophagy-mediated degradation of ingested tumors, leading to reduced antigen presentation and impaired CTL responses. Consistently, blockade of the TIM-4-AMPKalpha1-autophagy pathway augmented the antitumor effect of chemotherapeutics by enhancing tumor-specific CTL responses. Our finding provides insight into the immune tolerance mediated by phagocytosis of dying cells, and targeting of the TIM-4-AMPKalpha1 interaction constitutes a unique strategy for augmenting antitumor immunity and improving cancer chemotherapy. |
