CCR8-targeted specific depletion of clonally expanded Treg cells in tumor tissues evokes potent tumor immunity with long-lasting memory
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
Abstract
effector Tconvs, including tumor antigen-specific ones, that were more activated and less exhausted than those induced by PD-1 immune checkpoint blockade. Anti-CCR8 mAb treatment also evoked strong secondary immune responses against the same tumor cell line inoculated several months after tumor eradication, indicating that elimination of tumor-reactive multiclonal Tregs was sufficient to induce memory-type tumor-specific effector Tconvs. Despite induction of such potent tumor immunity, anti-CCR8 mAb treatment elicited minimal autoimmunity in mice, contrasting with systemic Treg depletion, which eradicated tumors but induced severe autoimmune disease. Thus, specific removal of clonally expanding Tregs in tumor tissues for a limited period by cell-depleting anti-CCR8 mAb treatment can generate potent tumor immunity with long-lasting memory and without deleterious autoimmunity.