Eradication of cancer cells by innate immune system Recognition by pattern recognition innate immune receptors

In harnessing the adaptive immune system, cancer immunotherapy is emerging as a successful treatment approach for patients with several types of advanced cancers, and has the potential to become the standard of care. The discovery of signal-transducing innate immune receptors and how they instruct the adaptive immune system has been a pillar of Immunology for the past two decades. Thus far, our understanding of how the innate immune receptors functions has primarily focused to their recognition of the components of invading pathogens such as bacteria and viruses. As such, whether and how these receptors recognize tumor cells remained totally unknown.

© 2014 Tadatsugu Taniguchi.
An innate immune receptor Dectin-1 recognizes N-glycan structures on cancer cells and activates Natural Killer (NK) cells through transcription factor IRF5.

In the laboratory of Tadatsugu Taniguchi (Project Professor, Director of Max Planck-The University of Tokyo Center for Integrative Inflammology), Shiho Chiba (Ph.D. student, Graduate School of Medicine), Hiroaki Ikushima (Project Assistant Professor and Max Planck Junior Fellow), Hiroshi Ueki (Ph.D. student, Graduate School of Medicine), and their colleagues at the Institute of Industrial Science of the University of Tokyo demonstrated that an innate immune receptor Dectin-1 serves an important role in the instruction of tumor cell-killing by natural killer (NK) cells. Expressed by macrophages and dendritic cells, Dectin-1 is well-known to recognize fungi-associated β-glucans. In demonstrating that this receptor can also recognize N-glycan structures overexpressed on tumor cells to activate anti-tumor innate immunity, this study is the first to demonstrate that an innate immune receptor contributes to tumor recognition.

These findings offer new insight into the anti-tumor innate immune system which has therapeutic implications for the development of novel cancer immunotherapy and/or cancer prevention.

This study was carried out in collaboration with Yoichiro Iwakura (Professor, Tokyo University of Science) and Shinobu Saijo (Associate Professor, Chiba University).

Paper

Shiho Chiba, Hiroaki Ikushima, Hiroshi Ueki, Hideyuki Yanai, Yoshitaka Kimura, Sho Hangai, Junko Nishio, Hideo Negishi, Tomohiko Tamura, Shinobu Saijo, Yoichiro Iwakura, Tadatsugu Taniguchi,
“ecognition of tumor cells by Dectin-1 orchestrates innate immune cells for anti-tumor responses”,
eLife Online Edition: 2014/8/22 (Japan time), doi: 10.7554/eLife.04177.
Article link

Links

Institute of Industrial Science

Department of Molecular Immunology, Institute of Industrial Science

Max Planck-The University of Tokyo Center for Integrative Inflammology