“The 90th of Stem Cell Biology and Regenerative Medicine Forum”
Date：Apr 14th (Thu) 2016
Time : 18:00 〜 19:30
Place：8th floor Hospital Building------------------------------------------------------------------------------------------------------------------------------------（Internal Speaker）
18:00-18:30 Ai Kawana-Tachikawa (AIDS Research Center, National Institute of Infectious
Diseases Department of AIDS Vaccine Development, IMSUT hospital)
Disruption of T cell immunity during chronic HIV-1 infection（External Speaker）
18:30-19:30 Norimitsu Kadowaki (Department of Internal Medicine Division ofHematology, Rheumatology and Respiratory Medicine Faculty of Medicine,Kagawa University)
Combination of targeted therapy and immunotherapy for cancer-------------------------------------------------------------------------------------------------------------------------------------

Hosted by Center for Stem Cell Biology and Regenerative Medicine---Information--＊ Please register attendance at the reception desk.
＊ Next forum will be held on Oct. I will contact you after the schedule is decided.
＊ Please contact tatsu-m@ims.u-tokyo.ac.jp, for Forum speaker recommendations

Disruption of T cell immunity during chronic HIV-1 infection
Ai Kawana-Tachikawa (AIDS Research Center, National Institute ofInfectious Diseases Department of AIDS Vaccine Development, IMSUThospital)
During chronic HIV-1 infection, T cells undergo cell intrinsic phenotypic andfunctional impairments that are coupled to increased pathogenesis. Phenotypicchanges of T cells during chronic HIV-1 infections have been characterized byskewed maturation and/or elevated levels of activation and exhaustion markers. Weand other researchers have previously showed reduction of specific cytokines
expression of T cells in HIV-1 non-controllers, which is associated withactivation/exhaustion status in memory T cells. However, molecular mechanisms
underlying the gene-specific reduction have not been revealed.
Epigenetic modification is a critical mechanism for stable gene expression,
especially DNA methylation mediated gene silencing. We observed that CpG sites
in the IL2 promoter of CD4+ T cells were highly methylated in HIV-1
non-controllers. Furthermore, the hyper-methylation status in the IL2 promoter wasassociated with CD57 expression, a marker of replicative senescence on T cells anda characteristic feature of T cells in HIV-1 infected individuals. These data suggestthat DNA methylation at the IL2 locus in CD4+ T cells is coupled toimmunosenescence and plays a critical role in the broad dysfunction that occurs inpolyclonal T cells during HIV-1 infection.

Combination of targeted therapy and immunotherapy for cancer
Norimitsu Kadowaki (Department of Internal Medicine Division ofHematology, Rheumatology and Respiratory Medicine Faculty of Medicine,
Kagawa University)
Targeted therapies and immunotherapies attack tumor cells through differentmechanisms. In addition, these therapies exhibit quick and delayed effects,respectively. Thus, combining both therapies complement each other. Furthermore,as targeted therapies may enhance functions of immune cells, both therapies areexpected to have synergistic effects.
A BCR-ABL tyrosine kinase inhibitor for chronic myeloid leukemia, dasatinib,
is capable of inhibiting a broad array of kinases in addition to ABL. Thus, dasatinib
may suppress activity of various immune cells. In fact, it has been reported that thedrug suppresses activation of T cells, NK cells in vitro. In addition, we previously
reported that dasatinib strongly suppresses IFNdendritic cells. Unexpectedly, however, dasatinib activates cytotoxic lymphocytes
in a substantial proportion of leukemia patients in vivo.
Here we tried to solve this conundrum, and found out an unexpected encounterof targeted therapy and immunotherapy for cancer.