1: AIM2 regulates anti-tumor immunity and is a viable therapeutic target for melanoma.
Science of the Month - September 2021
J Exp Med.
2021 Sep 6;218(9):e20200962. doi: 10.1084/jem.20200962. Epub 2021 Jul 29.
Keitaro Fukuda, Ken Okamura, Rebecca L Riding, Xueli Fan, Khashayar Afshari, Nazgol-Sadat Haddadi, Sean M McCauley, Mehmet H Guney, Jeremy Luban, Takeru Funakoshi, Tomonori Yaguchi, Yutaka Kawakami, Anastasia Khvorova, Katherine A Fitzgerald, John E Harris
Melanoma is a highly malignant skin cancer, and it is known that melanomas with poor CD8+ T-cell infiltration do not respond to immunotherapy. Therefore, there is a need for immunotherapies that can attract CD8+ T-cells to the melanoma. It was previously known that CD8+ T-cell tumor infiltration is promoted when tumor-infiltrating dendritic cells (TIDCs) recognize tumor-derived DNA via the cytoplasmic DNA sensor cGAS, activating the STING-type I interferon (IFN) signal. However, the function of the cytoplasmic DNA sensor AIM2 in TIDCs was unknown. We have shown that AIM2 in TIDCs has an immunosuppressive effect on cancer. By administering immunotherapy along with a dendritic cell vaccine that suppresses AIM2 within the tumor, we found that in addition to activating the STING-type I IFN signal, the production of IL-1β and IL-18 is suppressed. This, in turn, promotes tumor infiltration by CD8+ T-cells while inhibiting infiltration by regulatory T-cells, thereby enabling previously unresponsive melanomas to respond to immunotherapy. This suggests that therapies targeting AIM2 in TIDCs could become a novel immunotherapy for melanoma.
(Keitaro Fukuda, Department of Dermatology, 84th)
2: Current Status of and Perspectives on the Application of Marmosets in Neurobiology.
The common marmoset (Callithrix jacchus), a small primate, is a New World monkey native to Brazil that exhibits socio-behavioral characteristics common to humans and has excellent reproductive traits. In 2001, in close collaboration with the Central Institute for Experimental Animals, I began research using marmosets for brain science and regenerative medicine. Since then, we have successfully created models of spinal cord injury (2005) and Parkinson's disease (in submission) in marmosets, developed techniques for creating genetically modified marmosets (2009, 2016), determined the complete genome sequence (2016) (in collaboration with Dr. Erika Sasaki), and constructed an MRI brain atlas (Figure). These achievements have enhanced the reputation of the marmoset as an attractive experimental animal, creating a major global research trend. Particularly in the field of neuroscience, it has attracted significant attention as a model animal with a brain similar to that of humans and the potential for genetic modification. In this review article for the *Annual Review of Neuroscience*, I have summarized the current status and future prospects of marmoset neuroscience research, providing an overview of our understanding of brain structure and function and its application to disease models.
(Hideyuki Okano, Department of Physiology, 62nd)
Other Published Papers
1: Vitreous metabolomics profiling of proliferative diabetic retinopathy.
Diabetologia.
2021 Jan;64(1):70-82. doi: 10.1007/s00125-020-05309-y.
Yohei Tomita, Gael Cagnone, Zhongjie Fu, Bertan Cakir, Yumi Kotoda, Masaki Asakage, Yoshihiro Wakabayashi, Ann Hellström, Jean-Sébastien Joyal, Saswata Talukdar, Lois E H Smith, Yoshihiko Usui
2: Artificial intelligence-enabled fully automated detection of cardiac amyloidosis using electrocardiograms and echocardiograms.
Nature Communications.
Goto S, Mahara K, Beussink-Nelson L, Ikura H, Katsumata Y, Endo J, Gaggin HK, Shah SJ, Itabashi Y, MacRae CA, Deo RC.