The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Cish actively silences TCR signaling in CD8+ T cells to maintain tumor tolerance
Open accessAbstract
Improving the functional avidity of effector T cells is critical in overcoming inhibitory factors within the tumor microenvironment and eliciting tumor regression. We have found that Cish, a member of the suppressor of cytokine signaling (SOCS) family, is induced by TCR stimulation in CD8+ T cells and inhibits their functional avidity against tumors. Genetic deletion of Cish in CD8+ T cells enhances their expansion, functional avidity, and cytokine polyfunctionality, resulting in pronounced and durable regression of established tumors. Although Cish is commonly thought to block STAT5 activation, we found that the primary molecular basis of Cish suppression is through inhibition of TCR signaling. Cish physically interacts with the TCR intermediate PLC-γ1, targeting it for proteasomal degradation after TCR stimulation. These findings establish a novel targetable interaction that regulates the functional avidity of tumor-specific CD8+ T cells and can be manipulated to improve adoptive cancer immunotherapy.
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Cites
Innate and adaptive immune cells in the tumor microenvironment
Gajewski, T. F., Schreiber, H., & Fu, Y.-X. (2013) · Nature Immunology · doi:10.1038/ni.2703 · Cited by 4,148
Smith-Garvin, J. E., Koretzky, G. A., & Jordan, M. S. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132706 · Cited by 2,144
Effector and memory T-cell differentiation: implications for vaccine development
Kaech, S. M., Wherry, E. J., & Ahmed, R. (2002) · Nature Reviews Immunology · doi:10.1038/nri778 · Cited by 1,865
Adoptive immunotherapy for cancer: harnessing the T cell response
Restifo, N. P., Dudley, M. E., & Rosenberg, S. A. (2012) · Nature Reviews Immunology · doi:10.1038/nri3191 · Cited by 1,688
Self-citationSOCS proteins, cytokine signalling and immune regulation
Yoshimura, A., Naka, T., & Kubo, M. (2007) · Nature Reviews Immunology · doi:10.1038/nri2093 · Cited by 1,580
The SOCS box of SOCS-1 accelerates ubiquitin-dependent proteolysis of TEL-JAK2
Kamizono, S., Hanada, T., Yasukawa, H., Minoguchi, S., Kato, R., Minoguchi, M., Hattori, K., Hatakeyama, S., Yada, M., Morita, S., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m010074200 · Cited by 311
Babon, J. J., McManus, E. J., Yao, S., DeSouza, D. P., Mielke, L. A., Sprigg, N. S., Willson, T. A., Hilton, D. J., Nicola, N. A., Baca, M., et al. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.03.024 · Cited by 163
CISH and Susceptibility to Infectious Diseases
Khor, C. C., Vannberg, F. O., Chapman, S. J., Guo, H., Wong, S. H., Walley, A. J., Vukcevic, D., Rautanen, A., Mills, T. C., Chang, K.-C., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa0905606 · Cited by 136
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Cited by
A guide to cancer immunotherapy: from T cell basic science to clinical practice
Waldman, A. D., Fritz, J. M., & Lenardo, M. J. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-020-0306-5 · Cited by 4,154
Prospects for gene-engineered T cell immunotherapy for solid cancers
Klebanoff, C. A., Rosenberg, S. A., & Restifo, N. P. (2016) · Nature Medicine · doi:10.1038/nm.4015 · Cited by 365
Self-citationAtlas of the aging mouse brain reveals white matter as vulnerable foci
Hahn, O., Foltz, A. G., Atkins, M., Kedir, B., Moran-Losada, P., Guldner, I. H., Munson, C., Kern, F., Pálovics, R., Lu, N., et al. (2023) · Cell · doi:10.1016/j.cell.2023.07.027 · Cited by 213
Suppressors of cytokine signaling: Potential immune checkpoint molecules for cancer immunotherapy
Chikuma, S., Kanamori, M., Mise‐Omata, S., & Yoshimura, A. (2017) · Cancer Science · doi:10.1111/cas.13194 · Cited by 112
Gene Augmentation and Editing to Improve TCR Engineered T Cell Therapy against Solid Tumors
Lo Presti, V., Buitenwerf, F., van Til, N. P., & Nierkens, S. (2020) · Vaccines · doi:10.3390/vaccines8040733 · Cited by 14
Metadata
- Authors
- Palmer, D. C., Guittard, G. C., Franco, Z., Crompton, J. G., Eil, R. L., Patel, S. J., Ji, Y., Van Panhuys, N., Klebanoff, C. A., Sukumar, M., Clever, D., Chichura, A., Roychoudhuri, R., Varma, R., Wang, E., Gattinoni, L., Marincola, F. M., Balagopalan, L., Samelson, L. E., & Restifo, N. P.
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2015-11-02
- Volume
- 212
- Issue
- 12
- Pages
- 2095-2113
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2213269341
- Cited by
- 200
- References
- 9
- FWCI
- 5.36
- Type
- journal article
- Language
- en
- Open access
- green
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- The paper
- Palmer, D. C., Guittard, G. C., Franco, Z., Crompton, J. G., Eil, R. L., Patel, S. J., Ji, Y., Van Panhuys, N., Klebanoff, C. A., Sukumar, M., Clever, D., Chichura, A., Roychoudhuri, R., Varma, R., Wang, E., Gattinoni, L., Marincola, F. M., Balagopalan, L., Samelson, L. E., & Restifo, N. P. (2015). Cish actively silences TCR signaling in CD8+ T cells to maintain tumor tolerance. Journal of Experimental Medicine. https://doi.org/10.1084/jem.20150304
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