Immunity Article TIM-4 Glycoprotein-Mediated Degradation of Dying Tumor Cells by Autophagy Leads to Reduced Antigen Presentation and Increased Immune Tolerance Muhammad Baghdadi,1 Akihiro Yoneda,1 Tsunaki Yamashina,1 Hiroko Nagao,1 Yoshihiro Komohara,2 Shigenori Nagai,3 Hisaya Akiba,4 Marc Foretz,5,6,7 Hironori Yoshiyama,1 Ichiro Kinoshita,8 Hirotoshi Dosaka-Akita,8 Motohiro Takeya,2 Benoit Viollet,5,6,7 Hideo Yagita,4 and Masahisa Jinushi1,* 1Research Center for Infection-Associated Cancer, Institute for Genetic Medicine, Hokkaido University, Sapporo, 060-0815, Japan 2Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, 860-8556, Japan 3Department of Molecular Immunology, Tokyo Medical and Dental University, Tokyo, 113-8549, Japan 4Department of Immunology, Juntendo University School of Medicine, Tokyo, 113-8421, Japan 5INSERM, U1016, Institut Cochin, Paris, 75014, France 6CNRS, UMR8104, Paris, 75014, France 7Universite´ Paris Descartes, Sorbonne Paris Cite´ , 75014, France 8Department of Medical Oncology, Hokkaido University Graduate School of Medicine, Sapporo, 060-0815, Japan *Correspondence:
[email protected] http://dx.doi.org/10.1016/j.immuni.2013.09.014 SUMMARY is already skewed in favor of tumor progression. Recent evi- dences have clarified the critical role of intrinsic host immunity Phagocytosis of apoptotic cells by myeloid cells has in the regulation of tumor sensitivities to anticancer drugs. In been implicated in the maintenance of immune addition, the interactions between antigen-presenting cells homeostasis. In this study, we found that T cell (APCs) and T cells, which are regulated by various repertories immunoglobulin- and mucin domain-containing of costimulatory and coinhibitory molecules in tumor microenvi- molecule-4 (TIM-4) repressed tumor-specific immu- ronments, might impact tumor progression and anticancer drug nity triggered by chemotherapy-induced tumor cell resistance (Peggs et al., 2007).