MHC class I-associated phosphopeptides are the targets of memory-like immunity in leukemia

Research output: Contribution to journalArticlepeer-review

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MHC class I-associated phosphopeptides are the targets of memory-like immunity in leukemia. / Cobbold, Mark; De La Peña, Hugo; Norris, Andrew; Polefrone, Joy M; Qian, Jie; English, Ann Michelle; Cummings, Kara L; Penny, Sarah; Turner, James E; Cottine, Jennifer; Abelin, Jennifer G; Malaker, Stacy A; Zarling, Angela L; Huang, Hsing-Wen; Goodyear, Oliver; Freeman, Sylvie D; Shabanowitz, Jeffrey; Pratt, Guy; Craddock, Charles; Williams, Michael E; Hunt, Donald F; Engelhard, Victor H.

In: Science Translational Medicine, Vol. 5, No. 203, 18.09.2013, p. 203ra125.

Research output: Contribution to journalArticlepeer-review

Harvard

Cobbold, M, De La Peña, H, Norris, A, Polefrone, JM, Qian, J, English, AM, Cummings, KL, Penny, S, Turner, JE, Cottine, J, Abelin, JG, Malaker, SA, Zarling, AL, Huang, H-W, Goodyear, O, Freeman, SD, Shabanowitz, J, Pratt, G, Craddock, C, Williams, ME, Hunt, DF & Engelhard, VH 2013, 'MHC class I-associated phosphopeptides are the targets of memory-like immunity in leukemia', Science Translational Medicine, vol. 5, no. 203, pp. 203ra125. https://doi.org/10.1126/scitranslmed.3006061

APA

Cobbold, M., De La Peña, H., Norris, A., Polefrone, J. M., Qian, J., English, A. M., Cummings, K. L., Penny, S., Turner, J. E., Cottine, J., Abelin, J. G., Malaker, S. A., Zarling, A. L., Huang, H-W., Goodyear, O., Freeman, S. D., Shabanowitz, J., Pratt, G., Craddock, C., ... Engelhard, V. H. (2013). MHC class I-associated phosphopeptides are the targets of memory-like immunity in leukemia. Science Translational Medicine, 5(203), 203ra125. https://doi.org/10.1126/scitranslmed.3006061

Vancouver

Author

Cobbold, Mark ; De La Peña, Hugo ; Norris, Andrew ; Polefrone, Joy M ; Qian, Jie ; English, Ann Michelle ; Cummings, Kara L ; Penny, Sarah ; Turner, James E ; Cottine, Jennifer ; Abelin, Jennifer G ; Malaker, Stacy A ; Zarling, Angela L ; Huang, Hsing-Wen ; Goodyear, Oliver ; Freeman, Sylvie D ; Shabanowitz, Jeffrey ; Pratt, Guy ; Craddock, Charles ; Williams, Michael E ; Hunt, Donald F ; Engelhard, Victor H. / MHC class I-associated phosphopeptides are the targets of memory-like immunity in leukemia. In: Science Translational Medicine. 2013 ; Vol. 5, No. 203. pp. 203ra125.

Bibtex

@article{8dee679a4c3146baa584cc04152db7d7,
title = "MHC class I-associated phosphopeptides are the targets of memory-like immunity in leukemia",
abstract = "Deregulation of signaling pathways is a hallmark of malignant transformation. Signaling-associated phosphoproteins can be degraded to generate cancer-specific phosphopeptides that are presented by major histocompatibility complex (MHC) class I and II molecules and recognized by T cells; however, the contribution of these phosphoprotein-specific T cells to immune surveillance is unclear. We identified 95 phosphopeptides presented on the surface of primary hematological tumors and normal tissues, including 61 that were tumor-specific. Phosphopeptides were more prevalent on more aggressive and malignant samples. CD8(+) T cell lines specific for these phosphopeptides recognized and killed both leukemia cell lines and human leukocyte antigen-matched primary leukemia cells ex vivo. Notably, healthy individuals showed robust CD8(+) T cell responses against many of these phosphopeptides within the circulating memory compartment. This immunity was significantly reduced or absent in some leukemia patients. This reduction correlated with clinical outcome; however, immunity was restored after allogeneic stem cell transplantation. These results suggest that phosphopeptides may be targets of cancer immune surveillance in humans, and point to their importance for development of vaccine-based and T cell adoptive transfer immunotherapies.",
keywords = "CD8-Positive T-Lymphocytes, Cells, Cultured, Humans, Immunity, Leukemia, Major Histocompatibility Complex, Phosphopeptides, T-Lymphocytes",
author = "Mark Cobbold and {De La Pe{\~n}a}, Hugo and Andrew Norris and Polefrone, {Joy M} and Jie Qian and English, {Ann Michelle} and Cummings, {Kara L} and Sarah Penny and Turner, {James E} and Jennifer Cottine and Abelin, {Jennifer G} and Malaker, {Stacy A} and Zarling, {Angela L} and Hsing-Wen Huang and Oliver Goodyear and Freeman, {Sylvie D} and Jeffrey Shabanowitz and Guy Pratt and Charles Craddock and Williams, {Michael E} and Hunt, {Donald F} and Engelhard, {Victor H}",
year = "2013",
month = sep,
day = "18",
doi = "10.1126/scitranslmed.3006061",
language = "English",
volume = "5",
pages = "203ra125",
journal = "Science Translational Medicine",
issn = "1946-6234",
publisher = "American Association for the Advancement of Science",
number = "203",

}

RIS

TY - JOUR

T1 - MHC class I-associated phosphopeptides are the targets of memory-like immunity in leukemia

AU - Cobbold, Mark

AU - De La Peña, Hugo

AU - Norris, Andrew

AU - Polefrone, Joy M

AU - Qian, Jie

AU - English, Ann Michelle

AU - Cummings, Kara L

AU - Penny, Sarah

AU - Turner, James E

AU - Cottine, Jennifer

AU - Abelin, Jennifer G

AU - Malaker, Stacy A

AU - Zarling, Angela L

AU - Huang, Hsing-Wen

AU - Goodyear, Oliver

AU - Freeman, Sylvie D

AU - Shabanowitz, Jeffrey

AU - Pratt, Guy

AU - Craddock, Charles

AU - Williams, Michael E

AU - Hunt, Donald F

AU - Engelhard, Victor H

PY - 2013/9/18

Y1 - 2013/9/18

N2 - Deregulation of signaling pathways is a hallmark of malignant transformation. Signaling-associated phosphoproteins can be degraded to generate cancer-specific phosphopeptides that are presented by major histocompatibility complex (MHC) class I and II molecules and recognized by T cells; however, the contribution of these phosphoprotein-specific T cells to immune surveillance is unclear. We identified 95 phosphopeptides presented on the surface of primary hematological tumors and normal tissues, including 61 that were tumor-specific. Phosphopeptides were more prevalent on more aggressive and malignant samples. CD8(+) T cell lines specific for these phosphopeptides recognized and killed both leukemia cell lines and human leukocyte antigen-matched primary leukemia cells ex vivo. Notably, healthy individuals showed robust CD8(+) T cell responses against many of these phosphopeptides within the circulating memory compartment. This immunity was significantly reduced or absent in some leukemia patients. This reduction correlated with clinical outcome; however, immunity was restored after allogeneic stem cell transplantation. These results suggest that phosphopeptides may be targets of cancer immune surveillance in humans, and point to their importance for development of vaccine-based and T cell adoptive transfer immunotherapies.

AB - Deregulation of signaling pathways is a hallmark of malignant transformation. Signaling-associated phosphoproteins can be degraded to generate cancer-specific phosphopeptides that are presented by major histocompatibility complex (MHC) class I and II molecules and recognized by T cells; however, the contribution of these phosphoprotein-specific T cells to immune surveillance is unclear. We identified 95 phosphopeptides presented on the surface of primary hematological tumors and normal tissues, including 61 that were tumor-specific. Phosphopeptides were more prevalent on more aggressive and malignant samples. CD8(+) T cell lines specific for these phosphopeptides recognized and killed both leukemia cell lines and human leukocyte antigen-matched primary leukemia cells ex vivo. Notably, healthy individuals showed robust CD8(+) T cell responses against many of these phosphopeptides within the circulating memory compartment. This immunity was significantly reduced or absent in some leukemia patients. This reduction correlated with clinical outcome; however, immunity was restored after allogeneic stem cell transplantation. These results suggest that phosphopeptides may be targets of cancer immune surveillance in humans, and point to their importance for development of vaccine-based and T cell adoptive transfer immunotherapies.

KW - CD8-Positive T-Lymphocytes

KW - Cells, Cultured

KW - Humans

KW - Immunity

KW - Leukemia

KW - Major Histocompatibility Complex

KW - Phosphopeptides

KW - T-Lymphocytes

U2 - 10.1126/scitranslmed.3006061

DO - 10.1126/scitranslmed.3006061

M3 - Article

C2 - 24048523

VL - 5

SP - 203ra125

JO - Science Translational Medicine

JF - Science Translational Medicine

SN - 1946-6234

IS - 203

ER -