| Autor: |
Shibamiya, Asuka, Miyamoto-Nagai, Yurie, Koide, Shuhei, Oshima, Motohiko, Rizq, Ola, Aoyama, Kazumasa, Nakajima-Takagi, Yaeko, Kato, Rei, Kayamori, Kensuke, Isshiki, Yusuke, Oshima-Hasegawa, Nagisa, Muto, Tomoya, Tsukamoto, Shokichi, Takeda, Yusuke, Koyama-Nasu, Ryo, Chiba, Tetsuhiro, Honda, Hiroaki, Yokote, Koutaro, Iwama, Atsushi, Sakaida, Emiko |
| Předmět: |
|
| Zdroj: |
Cancer Immunology, Immunotherapy; Aug2023, Vol. 72 Issue 8, p2635-2648, 14p |
| Abstrakt: |
Dysfunctional anti-tumor immunity has been implicated in the pathogenesis of mature B cell neoplasms, such as multiple myeloma and B cell lymphoma; however, the impact of exhausted T cells on disease development remains unclear. Therefore, the present study investigated the features and pathogenetic significance of exhausted T cells using a mouse model of de novo mature B cell neoplasms, which is likely to show immune escape similar to human patients. The results revealed a significant increase in PD-1+ Tim-3− and PD-1+ Tim-3+ T cells in sick mice. Furthermore, PD-1+ Tim-3+ T cells exhibited direct cytotoxicity with a short lifespan, showing transcriptional similarities to terminally exhausted T cells. On the other hand, PD-1+ Tim-3− T cells not only exhibited immunological responsiveness but also retained stem-like transcriptional features, suggesting that they play a role in the long-term maintenance of anti-tumor immunity. In PD-1+ Tim-3− and PD-1+ Tim-3+ T cells, the transcription factors Tox and Nr4a2, which reportedly contribute to the progression of T cell exhaustion, were up-regulated in vivo. These transcription factors were down-regulated by IMiDs in our in vitro T cell exhaustion analyses. The prevention of excessive T cell exhaustion may maintain effective anti-tumor immunity to cure mature B cell neoplasms. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
Full text from SpringerLink