@article{4d79e89f1f334e08a052ab740e865464,
title = "Resident memory CD8+ T cells in regional lymph nodes mediate immunity to metastatic melanoma",
abstract = "The nature of the anti-tumor immune response changes as primary tumors progress and metastasize. We investigated the role of resident memory (Trm) and circulating memory (Tcirm) cells in anti-tumor responses at metastatic locations using a mouse model of melanoma-associated vitiligo. We found that the transcriptional characteristics of tumor-specific CD8+ T cells were defined by the tissue of occupancy. Parabiosis revealed that tumor-specific Trm and Tcirm compartments persisted throughout visceral organs, but Trm cells dominated lymph nodes (LNs). Single-cell RNA-sequencing profiles of Trm cells in LN and skin were distinct, and T cell clonotypes that occupied both tissues were overwhelmingly maintained as Trm in LNs. Whereas Tcirm cells prevented melanoma growth in the lungs, Trm afforded long-lived protection against melanoma seeding in LNs. Expanded Trm populations were also present in melanoma-involved LNs from patients, and their transcriptional signature predicted better survival. Thus, tumor-specific Trm cells persist in LNs, restricting metastatic cancer.",
keywords = "Cancer, CD69, CD8 T cells, CXCR6, parabiosis, scRNA-seq, TCR, Trm, TRP-2, vitiligo",
author = "Molodtsov, {Aleksey K.} and Nikhil Khatwani and Vella, {Jennifer L.} and Lewis, {Kathryn A.} and Yanding Zhao and Jichang Han and Sullivan, {Delaney E.} and Searles, {Tyler G.} and Preiss, {Nicholas K.} and Shabaneh, {Tamer B.} and Peisheng Zhang and Hawkes, {Aaron R.} and Malik, {Brian T.} and Kolling, {Fred W.} and Usherwood, {Edward J.} and Wong, {Sandra L.} and Phillips, {Joseph D.} and Keisuke Shirai and Angeles, {Christina V.} and Shaofeng Yan and Curiel, {Tyler J.} and Huang, {Yina H.} and Chao Cheng and Turk, {Mary Jo}",
note = "Funding Information: Keep on jammin, MCVC. We thank David Findley, Kayla Fay, Fatima Haider, and Brian Highhouse for their help in acquiring patient specimens and DartLab for assistance with sample processing and flow cytometry. This work was supported by NIH R01 CA225028 to M.J.T. NIH R01 CA205965 to M.J.T. and T.J.C. NIH R21 CA227996 to C.C. a Cancer Prevention Research Institute of Texas grant (CPRIT RR180061) to C.C. (C.C. is a CPRIT Scholar in Cancer Research), NIH F31CA232554 to A.K.M. The O. Ross McIntyre, M.D. Endowment, Knights of the York Cross of Honor and Munck-Pfefferkorn Research Funds to M.J.T. NIH R01 CA054174 and CA231325 and an Owens Foundation grant to T.J.C. and support from 5P30 CA023108-40 (Immune Monitoring Shared Resource). Graphical abstract was created with BioRender.com. A.K.M. N.K. Y.H.H. M.J.T. and C.C. contributed to formulation of theory and prediction of the experimental data. A.K.M. M.J.T. and N.K. contributed to experimental conception and design. A.K.M. K.A.L. Y.Z. J.L.V. J.H. A.R.H. P.Z. D.E.S. B.T.M. F.W.K. S.Y. N.K. T.G.S. E.J.U. N.K.P. C.C. M.J.T. and Y.H.H. contributed to acquisition, analysis, and/or interpretation of data. S.Y. K.S. J.D.P. and S.L.W. identified study patients and provided human specimens. A.K.M. N.K. T.B.S. Y.H.H. C.V.A. T.J.C. C.C. and M.J.T. contributed to drafting the article and revising it critically for important intellectual content. M.J.T. T.J.C. and C.C. contributed funding for this work. Authors declare no competing interests. We worked to ensure gender balance in the recruitment of human subjects. One or more of the authors of this paper self-identifies as an underrepresented ethnic minority in science. One or more of the authors of this paper received support from a program designed to increase minority representation in science. Funding Information: Keep on jammin, MCVC. We thank David Findley, Kayla Fay, Fatima Haider, and Brian Highhouse for their help in acquiring patient specimens and DartLab for assistance with sample processing and flow cytometry. This work was supported by NIH R01 CA225028 to M.J.T., NIH R01 CA205965 to M.J.T. and T.J.C., NIH R21 CA227996 to C.C., a Cancer Prevention Research Institute of Texas grant ( CPRIT RR180061 ) to C.C. (C.C. is a CPRIT Scholar in Cancer Research), NIH F31CA232554 to A.K.M., The O. Ross McIntyre, M.D. Endowment, Knights of the York Cross of Honor and Munck-Pfefferkorn Research Funds to M.J.T., NIH R01 CA054174 and CA231325 and an Owens Foundation grant to T.J.C., and support from 5P30 CA023108-40 (Immune Monitoring Shared Resource). Graphical abstract was created with BioRender.com . Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = sep,
day = "14",
doi = "10.1016/j.immuni.2021.08.019",
language = "English (US)",
volume = "54",
pages = "2117--2132.e7",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "9",
}