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| タイトル | CXCR4 induces memory formation over exhaustion in CAR-T cells to achieve durable leukemia targeting. |
|---|---|
| ジャーナル・号・ページ | Nat Commun, Vol. 17, Issue 1, Page 101, Year 2026 |
| 掲載日 | 2026年1月26日 |
著者 | Ari Itoh-Nakadai / Minggao Liang / Michiho Shindo / Chen Bibi / Mariko Tomizawa-Murasawa / Saera Fujiki / Akiko Kaneko / Emi Kanamaru / Mari Hashimoto / Hiroshi Kajita / Yoshinari Ando / Miki Kojima / Jonathan Moody / Makoto Iwasaki / Shinsuke Takagi / Ryo Nakagawa / Saumya Agrawal / Hanae Amitani-Iijima / Kaori Sato / Yuriko Sorimachi / Nahoko Suzuki / Takehiro Fukami / Kazuharu Hanada / Satoshi Morita / Kazushige Katsura / Takehisa Matsumoto / Maiko Kobayashi / Masahiko Kato / Yasuyuki Negishi / Mikako Shirouzu / Yuho Najima / Keiyo Takubo / Chung Chau Hon / Naoyuki Uchida / Shuichi Taniguchi / Yukihide Momozawa / Piero Carninci / Leonard D Shultz / Yoriko Saito / Michiel de Hoon / Jay W Shin / Fumihiko Ishikawa / ![]() |
| PubMed 要旨 | Chimeric antigen receptor (CAR)-T cell therapy has transformed the treatment of B-cell malignancies, but its success in acute myeloid leukemia (AML) remains limited. Durable responses depend on the ...Chimeric antigen receptor (CAR)-T cell therapy has transformed the treatment of B-cell malignancies, but its success in acute myeloid leukemia (AML) remains limited. Durable responses depend on the formation of long-lived memory T cells, whereas T cell exhaustion contributes to non-response and relapse. In patients with AML who achieved remission after cord blood transplantation, we here first observe enrichment of memory T cells with high expression of the chemokine receptor CXCR4. Next, we show that engineering CAR-T cells to co-express CXCR4 enhances their persistence and anti-leukemic activity in patient-derived xenograft models. Using single-cell profiling and metabolic analysis, we find that CXCR4 promotes memory-associated transcriptional programs, reduces exhaustion, and supports oxidative metabolism. These effects are observed with CAR-T cells targeting CD25 or CD96 as AML-associated targets. Our results indicate that CXCR4 strengthens CAR-T cell memory and durability, offering a strategy to improve immunotherapy outcomes in AML and beyond. |
リンク | Nat Commun / PubMed:41587986 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.97 Å |
| 構造データ | EMDB-62427, PDB-9kmc: |
| 化合物 | ![]() ChemComp-NAG: |
| 由来 |
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キーワード | IMMUNE SYSTEM / CYTOKINE |
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