The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.
PD-1 identifies the patient-specific CD8+ tumor-reactive repertoire infiltrating human tumors
Open accessAbstract
Adoptive transfer of tumor-infiltrating lymphocytes (TILs) can mediate regression of metastatic melanoma; however, TILs are a heterogeneous population, and there are no effective markers to specifically identify and select the repertoire of tumor-reactive and mutation-specific CD8⁺ lymphocytes. The lack of biomarkers limits the ability to study these cells and develop strategies to enhance clinical efficacy and extend this therapy to other malignancies. Here, we evaluated unique phenotypic traits of CD8⁺ TILs and TCR β chain (TCRβ) clonotypic frequency in melanoma tumors to identify patient-specific repertoires of tumor-reactive CD8⁺ lymphocytes. In all 6 tumors studied, expression of the inhibitory receptors programmed cell death 1 (PD-1; also known as CD279), lymphocyte-activation gene 3 (LAG-3; also known as CD223), and T cell immunoglobulin and mucin domain 3 (TIM-3) on CD8⁺ TILs identified the autologous tumor-reactive repertoire, including mutated neoantigen-specific CD8⁺ lymphocytes, whereas only a fraction of the tumor-reactive population expressed the costimulatory receptor 4-1BB (also known as CD137). TCRβ deep sequencing revealed oligoclonal expansion of specific TCRβ clonotypes in CD8⁺PD-1⁺ compared with CD8⁺PD-1- TIL populations. Furthermore, the most highly expanded TCRβ clonotypes in the CD8⁺ and the CD8⁺PD-1⁺ populations recognized the autologous tumor and included clonotypes targeting mutated antigens. Thus, in addition to the well-documented negative regulatory role of PD-1 in T cells, our findings demonstrate that PD-1 expression on CD8⁺ TILs also accurately identifies the repertoire of clonally expanded tumor-reactive cells and reveal a dual importance of PD-1 expression in the tumor microenvironment.
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Cites
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Self-citation
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Elements of cancer immunity and the cancer–immune set point
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Approaches to treat immune hot, altered and cold tumours with combination immunotherapies
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Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential
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Metadata
- Authors
- Gros, A., Robbins, P. F., Yao, X., Li, Y. F., Turcotte, S., Tran, E., Wunderlich, J. R., Mixon, A., Farid, S., Dudley, M. E., Hanada, K.-I., Almeida, J. R., Darko, S., Douek, D. C., Yang, J. C., & Rosenberg, S. A.
- Venue
- Journal of Clinical Investigation
- Published
- 2014-03-25
- Volume
- 124
- Issue
- 5
- Pages
- 2246-2259
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W1980137951
- Cited by
- 1,111
- References
- 15
- FWCI
- 40.79
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Gros, A., Robbins, P. F., Yao, X., Li, Y. F., Turcotte, S., Tran, E., Wunderlich, J. R., Mixon, A., Farid, S., Dudley, M. E., Hanada, K.-I., Almeida, J. R., Darko, S., Douek, D. C., Yang, J. C., & Rosenberg, S. A. (2014). PD-1 identifies the patient-specific CD8+ tumor-reactive repertoire infiltrating human tumors. Journal of Clinical Investigation. https://doi.org/10.1172/jci73639
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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.
