RT Journal Article
SR Electronic
T1 A reservoir of stem-like CD8 T cells in the tumor-draining lymph node maintains the ongoing anti-tumor immune response
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.01.27.428467
DO 10.1101/2021.01.27.428467
A1 Kelli A. Connolly
A1 Manik Kuchroo
A1 Aarthi Venkat
A1 Achia Khatun
A1 Jiawei Wang
A1 Ivana William
A1 Noah Hornick
A1 Brittany Fitzgerald
A1 Martina Damo
A1 Moujtaba Y. Kasmani
A1 Can Cui
A1 Eric Fagerberg
A1 Isabel Monroy
A1 Amanda Hutchins
A1 Julie F Cheung
A1 Gena G. Foster
A1 Dylan L. Mariuzza
A1 Hongyu Zhao
A1 Weiguo Cui
A1 Smita Krishnaswamy
A1 Nikhil S. Joshi
YR 2021
UL http://biorxiv.org/content/early/2021/01/27/2021.01.27.428467.abstract
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.