The pathogenetic significance of exhausted T cells in a mouse model of mature B cell neoplasms

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.

Automated summary

The study investigated the characteristics and significance of exhausted T cells in mature B cell neoplasms. The results showed an increase in PD-1(+) Tim-3(-) and PD-1(+) Tim-3(+) T cells in sick mice. PD-1(+) Tim-3(+) T cells exhibited cytotoxicity and short lifespan, resembling terminally exhausted T cells, while PD-1(+) Tim-3(-) T cells retained immunological responsiveness and stem-like features. The prevention of excessive T cell exhaustion may maintain effective anti-tumor immunity in mature B cell neoplasms.