| Autor: |
Aarthi Venkat, Brittany Fitzgerald, Martina Damo, Achia Khatun, Nikhil S. Joshi, Isabel Monroy, Amanda Hutchins, Weiguo Cui, Kelli A. Connolly, Can Cui, Moujtaba Y. Kasmani, Manik Kuchroo, Smita Krishnaswamy |
| Rok vydání: |
2020 |
| Předmět: |
|
| Zdroj: |
SSRN Electronic Journal. |
| ISSN: |
1556-5068 |
| DOI: |
10.2139/ssrn.3640763 |
| Popis: |
Intratumoral stem-like CD8+ T cells (TSL) are necessary for immunotherapeutic efficacy. Yet, tumors are rich in signals driving terminal differentiation of TSL cells into exhausted T cells. Using the “KP-NINJA” lung tumor model, we determined that tumor-specific TSL cells terminally differentiate in tumors, but that they are maintained by a reservoir of TSL cells from the tumor-draining lymph node (dLN). By tracing clones of tumor-specific CD8+ T cells using single-cell RNA/TCRseq, we found that dLN TSL cells were the developmental precursors of the more differentiated intratumoral T cell populations. Moreover, dLN TSL cells were developmentally stable over the disease course and blocking egress from dLNs resulted in a decrease in intratumoral TSL cells. Thus, we propose that the dLN reservoir protects the overall tumor-specific T cell population from terminal differentiation, allowing for prolonged responses under conditions of chronic antigen exposure. Future immunotherapeutic strategies could leverage this reservoir for anti-tumor effects. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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