PT  - JOURNAL ARTICLE
AU  - Kelli A. Connolly
AU  - Manik Kuchroo
AU  - Aarthi Venkat
AU  - Achia Khatun
AU  - Jiawei Wang
AU  - Ivana William
AU  - Noah Hornick
AU  - Brittany Fitzgerald
AU  - Martina Damo
AU  - Moujtaba Y. Kasmani
AU  - Can Cui
AU  - Eric Fagerberg
AU  - Isabel Monroy
AU  - Amanda Hutchins
AU  - Julie F Cheung
AU  - Gena G. Foster
AU  - Dylan L. Mariuzza
AU  - Hongyu Zhao
AU  - Weiguo Cui
AU  - Smita Krishnaswamy
AU  - Nikhil S. Joshi
TI  - A reservoir of stem-like CD8 T cells in the tumor-draining lymph node maintains the ongoing anti-tumor immune response
AID  - 10.1101/2021.01.27.428467
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.01.27.428467
4099  - http://biorxiv.org/content/early/2021/01/27/2021.01.27.428467.short
4100  - http://biorxiv.org/content/early/2021/01/27/2021.01.27.428467.full
AB  - “Stem-like” TCF1+ CD8+ T cells (TSL) are necessary for long-term maintenance of T cell responses and the efficacy of immunotherapy but, as tumors contain signals that should drive T-cell terminal-differentiation, how these cells are maintained in tumors remains unclear. We found that a small number of TCF1+ tumor-specific CD8+ T cells were present in tumors throughout development. Yet, most intratumoral T cells differentiated as tumors progressed, corresponding with an immunologic shift in the tumor microenvironment (TME) from “hot” to “cold”. By contrast, most tumor-specific CD8+ T cells in tumor-draining lymph nodes (dLNs) had functions and gene expression signatures similar to TSL from chronic LCMV infection and this population was stable over time, despite the changes in the TME. dLN T cells were the precursors of their more-differentiated intratumoral counterparts, and maintenance of TCF1 by intratumoral T cells required continuous migration from dLNs. Finally, TSL CD8 T cells were also present in LNs from lung adenocarcinoma patients, suggesting this population is also relevant in human disease. Thus, we propose that the dLN TSL reservoir has a critical function during tumor development in sustaining antitumor T cells during tumor development and protecting them from the terminal differentiation that occurs in the TME.Competing Interest StatementThe authors have declared no competing interest.