title: Spatially selective depletion of tumor-associated regulatory T cells with near-infrared photoimmunotherapy.
abstract: Current immunotherapies for cancer seek to modulate the balance among different immune cell populations, thereby promoting antitumor immune responses. However, because these are systemic therapies, they often cause treatment-limiting autoimmune adverse effects. It would be ideal to manipulate the balance between suppressor and effector cells within the tumor without disturbing homeostasis elsewhere in the body. CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) are well-known immunosuppressor cells that play a key role in tumor immunoevasion and have been the target of systemic immunotherapies. We used CD25-targeted near-infrared photoimmunotherapy (NIR-PIT) to selectively deplete Tregs, thus activating CD8 T and natural killer cells and restoring local antitumor immunity. This not only resulted in regression of the treated tumor but also induced responses in separate untreated tumors of the same cell line derivation. We conclude that CD25-targeted NIR-PIT causes spatially selective depletion of Tregs, thereby providing an alternative approach to cancer immunotherapy.
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1002, USA. Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Sato
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1002, USA.
authors.forename: Noriko
authors.initials: N
authors.lastname: Sato
authors.affiliation: Image Probe Development Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-3372, USA.
authors.forename: Biying
authors.initials: B
authors.lastname: Xu
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1002, USA.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1002, USA.
authors.forename: Tadanobu
authors.initials: T
authors.lastname: Nagaya
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1002, USA.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Choyke
authors.affiliation: Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Hasegawa
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1002, USA. kobayash@mail.nih.gov.
authors.forename: Hisataka
authors.initials: H
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000096:biosynthesis; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion / Q000379:methods*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000628:therapy*; D010789:Phototherapy / Q000379:methods*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D057170:Translational Research, Biomedical
chemical_list: D016207:Cytokines; C000611649:IFNG protein, mouse; C508018:Il2ra protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D007371:Interferon-gamma