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Cited by 420

The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.

A Distinct Gene Module for Dysfunction Uncoupled from Activation in Tumor-Infiltrating T Cells

Open access
Singer, Meromit, Wang, Chao, Cong, Le, Marjanovic, Nemanja D., Kowalczyk, Monika S., Zhang, Huiyuan, Nyman, Jackson, Sakuishi, Kaori, Kurtulus, Sema, Gennert, David, Xia, Junrong, Kwon, John Y.H., Nevin, James, Herbst, Rebecca H., Yanai, Itai, Rozenblatt-Rosen, Orit, Kuchroo, Vijay K., Regev, Aviv, Anderson, Ana C.·2016·Cell

Abstract

Summary Reversing the dysfunctional T cell state that arises in cancer and chronic viral infections is the focus of therapeutic interventions; however, current therapies are effective in only some patients and some tumor types. To gain a deeper molecular understanding of the dysfunctional T cell state, we analyzed population and single-cell RNA profiles of CD8+ tumor-infiltrating lymphocytes (TILs) and used genetic perturbations to identify a distinct gene module for T cell dysfunction that can be uncoupled from T cell activation. This distinct dysfunction module is downstream of intracellular metallothioneins that regulate zinc metabolism and can be identified at single-cell resolution. We further identify Gata-3, a zinc-finger transcription factor in the dysfunctional module, as a regulator of dysfunction, and use CRISPR/Cas9 genome editing to show that it drives a dysfunctional phenotype in CD8+ TILs. Our results open novel avenues for targeting dysfunctional T cell states, while leaving activation programs intact.

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Crossref · 10.1016/j.cell.2016.08.052

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Metadata

Authors
Singer, M., Wang, C., Cong, L., Marjanovic, N. D., Kowalczyk, M. S., Zhang, H., Nyman, J., Sakuishi, K., Kurtulus, S., Gennert, D., Xia, J., Kwon, J. Y. H., Nevin, J., Herbst, R. H., Yanai, I., Rozenblatt-Rosen, O., Kuchroo, V. K., Regev, A., & Anderson, A. C.
Venue
Cell
Publisher
Elsevier BV
Published
2016-09
Volume
166
Issue
6
Pages
1500-1511.e9
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2510606169
Cited by
420
References
39
FWCI
19.93
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: A Distinct Gene Module for Dysfunction Uncoupled from Activation in Tumor-Infiltrating T Cells. https://app.cochat.ai/papers/10.1016/j.cell.2016.08.052
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Singer, M., Wang, C., Cong, L., Marjanovic, N. D., Kowalczyk, M. S., Zhang, H., Nyman, J., Sakuishi, K., Kurtulus, S., Gennert, D., Xia, J., Kwon, J. Y. H., Nevin, J., Herbst, R. H., Yanai, I., Rozenblatt-Rosen, O., Kuchroo, V. K., Regev, A., & Anderson, A. C. (2016). A Distinct Gene Module for Dysfunction Uncoupled from Activation in Tumor-Infiltrating T Cells. Cell. https://doi.org/10.1016/j.cell.2016.08.052

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.