Open AccessCCR8-targeted specific depletion of clonally expanded Treg cells in tumor tissues evokes potent tumor immunity with long-lasting memory
Author(s) -
Yujiro Kidani,
Wataru Nogami,
Yoshiaki Yasumizu,
Atsunari Kawashima,
Atsushi Tanaka,
Yudai Sonoda,
Yumi Tona,
Kunitaka Nashiki,
Reimi Matsumoto,
Makoto Hagiwara,
Motonao Osaki,
Keiji Dohi,
Takayuki Kanazawa,
Azumi Ueyama,
Manabu Yoshikawa,
Tetsuya Yoshida,
Mitsunobu Matsumoto,
Kanji Hojo,
Satomi Shiome,
Hiroshi Yoshida,
Michinari Hirata,
Miya Haruna,
Yurika Nakamura,
Daisuke Motooka,
Daisuke Okuzaki,
Yoshihiro Sugiyama,
Makoto Kinoshita,
Tatsusada Okuno,
Taigo Kato,
Koji Hatano,
Mamoru Uemura,
Ryoichi Imamura,
Kunihiko Yokoi,
Atsushi Tanemura,
Yasushi Shintani,
Tadashi Kimura,
Norio omura,
Hisashi Wada,
Masaki Mori,
Yuichiro Doki,
Naganari Ohkura,
Shimon Sakaguchi
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2114282119
Subject(s) - biology , immunology , effector , foxp3 , cancer research , immunity , chemokine , immunotherapy , immune system
Significance Immunosuppressive Foxp3-expressing regulatory T cells (Tregs) in tumor tissues are assumed to be clonally expanding via recognizing tumor-associated antigens. By single-cell RNA sequencing, we have searched for the molecules that are specifically expressed by such multiclonal tumor Tregs, but not by tumor-infiltrating effector T cells or natural Tregs in other tissues. The search revealed the chemokine receptor CCR8 as a candidate. Treatment of tumor-bearing mice with cell-depleting anti-CCR8 antibody indeed selectively removed multiclonal tumor Tregs without affecting effector T cells or tissue Tregs, eradicating established tumors with induction of potent tumor-specific effector/memory T cells and without activating autoimmune T cells. Thus, specific depletion of clonally expanding tumor Tregs is clinically instrumental for evoking effective tumor immunity without autoimmune adverse effects.