CCR8-targeted specific depletion of clonally expanded Treg cells in tumor tissues evokes potent tumor immunity with long-lasting memory
| Autor: | Yujiro Kidani, Wataru Nogami, Yoshiaki Yasumizu, Atsunari Kawashima, Atsushi Tanaka, Yudai Sonoda, Yumi Tona, Kunitaka Nashiki, Reimi Matsumoto, Masaki Hagiwara, Motonao Osaki, Keiji Dohi, Takayuki Kanazawa, Azumi Ueyama, Mai Yoshikawa, Tetsuya Yoshida, Mitsunobu Matsumoto, Kanji Hojo, Satomi Shinonome, Hiroshi Yoshida, Michinari Hirata, Miya Haruna, Yamami Nakamura, Daisuke Motooka, Daisuke Okuzaki, Yasuko Sugiyama, Makoto Kinoshita, Tatsusada Okuno, Taigo Kato, Koji Hatano, Motohide Uemura, Ryoichi Imamura, Kazunori Yokoi, Atsushi Tanemura, Yasushi Shintani, Tadashi Kimura, Norio Nonomura, Hisashi Wada, Masaki Mori, Yuichiro Doki, Naganari Ohkura, Shimon Sakaguchi |
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| Rok vydání: | 2022 |
| Předmět: |
Multidisciplinary
Cell- and Tissue-Based Therapy Antibodies Monoclonal Cell Differentiation Forkhead Transcription Factors hemic and immune systems chemical and pharmacologic phenomena T-Lymphocytes Regulatory Receptors CCR8 Gene Expression Regulation Neoplastic Mice Neoplasms Biomarkers Tumor Animals Humans Immunologic Memory Gene Deletion |
| Zdroj: | Proceedings of the National Academy of Sciences. 119 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | SignificanceImmunosuppressive 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. |
| Databáze: | OpenAIRE |
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