The DOI matches its Crossref record; 68 of the 68 references it cites were found in a registry or an index.
T cell costimulatory receptor CD28 is a primary target for PD-1–mediated inhibition
Open accessPublished version of a preprint
Abstract
Immunotherapeutic PD-1–targeted therapies require CD28 to promote cancer cell killing.
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In the citing paper
“Ligation of PD-1 with its ligands programmed death-ligand 1 or 2 (PD-L1 or PD-L2) induces tyrosine phosphorylation of the PD-1 cytoplasmic domain by phosphorylating kinase Lck and subsequent recruitment of cytosolic tyrosine phosphatase SHP-2 and PD-1-associated SHP-2 preferentially dephosphorylates CD28 and suppresses CD28 costimulatory signaling leading to restrained effector T cell function (49”
From mRNA vaccine with unmodified uridine induces robust type I interferon-dependent anti-tumor immunity in a melanoma model (2022) · cites this paper as [49]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Overcoming such checkpoints through the use of therapeutic antibodies targeting the CTLA-4, PD-1, or PD-L1 cell-surface receptors was shown to be instrumental in promoting anti-tumor T cell responses in mice and in cancer patients”
From LXR/ApoE Activation Restricts Innate Immune Suppression in Cancer (2018) · cites this paper as Hui et al., 2017
Experimental — accuracy not yet measuredIn the citing paper
“SHP2 also has effects on parallel pathways (e.g., JAK/STAT signaling) and is implicated as an effector of inhibitory signaling by PD-1 and some other immune checkpoint receptors (Hui et al., 2017; Peled et al., 2018; Yokosuka et al., 2012).”
From SHP2 inhibition diminishes KRASG12C cycling and promotes tumor microenvironment remodeling (2021) · cites this paper as Hui et al., 2017
In the citing paper
“Among these, CD28 has recently been found to be the primary target (45).”
From Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations (2018) · cites this paper as [45]
In the citing paper
“The requirement for both T cell co-stimulation and IL-12 to achieve maximal IFN-γ response likely reflected the need of CD28 to rescue exhausted CD8+ T cells, and possibly also the role of PD-1 in limiting CD28-mediated co-stimulation (Kamphorst et al., 2017; Hui et al., 2017).”
From Successful Anti-PD-1 Cancer Immunotherapy Requires T Cell-Dendritic Cell Crosstalk Involving the Cytokines IFN-γ and IL-12 (2018) · cites this paper as Hui et al., 2017
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Citations
Cites
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989
Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review
Wanchoo, R., Karam, S., Uppal, N. N., Barta, V. S., Deray, G., Devoe, C., Launay‐Vacher, V., Jhaveri, K. D., & on behalf of Cancer and Kidney International Network Workgroup on Immune Checkpoint Inhibitors (2017) · American Journal of Nephrology · doi:10.1159/000455014 · Cited by 15,320
The blockade of immune checkpoints in cancer immunotherapy
Pardoll, D. M. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3239 · Cited by 13,838
Safety, activity, and immune correlates of anti–PD-1 antibody in cancer
Topalian, S. L., Hodi, F. S., Brahmer, J. R., Gettinger, S. N., Smith, D. C., McDermott, D. F., Powderly, J. D., Carvajal, R. D., Sosman, J. A., Atkins, M. B., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200690 · Cited by 12,628
Oncology meets immunology: the cancer-immunity cycle.
Chen, D. S., & Mellman, I. (2013) · Immunity · doi:10.1016/j.immuni.2013.07.012 · Cited by 6,929
Self-citationPD-1 and Its Ligands in Tolerance and Immunity
Keir, M. E., Butte, M. J., Freeman, G. J., & Sharpe, A. H. (2008) · Annual Review of Immunology · doi:10.1146/annurev.immunol.26.021607.090331 · Cited by 5,378
Freeman, G. J., Long, A. J., Iwai, Y., Bourque, K., Chernova, T., Nishimura, H., Fitz, L. J., Malenkovich, N., Okazaki, T., Byrne, M. C., et al. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.7.1027 · Cited by 5,294
Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients
Herbst, R. S., Soria, J.-C., Kowanetz, M., Fine, G. D., Hamid, O., Gordon, M. S., Sosman, J. A., McDermott, D. F., Powderly, J. D., Gettinger, S. N., et al. (2014) · Nature · doi:10.1038/nature14011 · Cited by 5,231
Self-citationTumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion
Dong, H., Strome, S. E., Salomao, D. R., Tamura, H., Hirano, F., Flies, D. B., Roche, P. C., Lu, J., Zhu, G., Tamada, K., et al. (2002) · Nature Medicine · doi:10.1038/nm730 · Cited by 5,025
The future of immune checkpoint therapy
Sharma, P., & Allison, J. P. (2015) · Science · doi:10.1126/science.aaa8172 · Cited by 4,878
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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
Approaches to treat immune hot, altered and cold tumours with combination immunotherapies
Galon, J., & Bruni, D. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-018-0007-y · Cited by 3,520
Fundamental Mechanisms of Immune Checkpoint Blockade Therapy
Wei, S. C., Duffy, C. R., & Allison, J. P. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-0367 · Cited by 3,088
Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response
Chen, G., Huang, A. C., Zhang, W., Zhang, G., Wu, M., Xu, W., Yu, Z., Yang, J., Wang, B., Sun, H., et al. (2018) · Nature · doi:10.1038/s41586-018-0392-8 · Cited by 2,813
Self-citationRegulation and Function of the PD-L1 Checkpoint
Sun, C., Mezzadra, R., & Schumacher, T. N. (2018) · Immunity · doi:10.1016/j.immuni.2018.03.014 · Cited by 2,248
Metadata
- Authors
- Hui, E., Cheung, J., Zhu, J., Su, X., Taylor, M. J., Wallweber, H. A., Sasmal, D. K., Huang, J., Kim, J. M., Mellman, I., & Vale, R. D.
- Affiliations
- Howard Hughes Medical Institute (US)
- Genentech (US)
- University of Chicago (US)
- Corresponding author
- Mellman, Ira
- Vale, Ronald D.
- ORCID
- Venue
- Science
- Published
- 2017-03-31
- Volume
- 355
- Issue
- 6332
- Pages
- 1428-1433
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC6286077
- OpenAlex
- W2592133876
- Cited by
- 1,689
- References
- 68
- Citations by year
- 2026: 121 · 2025: 158 · 2024: 201 · 2023: 203 · 2022: 193 · 2021: 218 · 2020: 224 · 2019: 159 · 2018: 143 · 2017: 63
- FWCI
- 70.99
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Science (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Funders
- Chicago Biomedical Consortium
- NIH (R21AI120010, R00AI106941)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Keywords
- PD-1, CD28, PD-L1, T cell costimulation, T cell receptor signaling, SHP2, receptor dephosphorylation, T cell activation, anti-PD-1 therapy, cancer immunotherapy
- MeSH terms
- Animals, Humans, Immunotherapy, Lymphocyte Activation, Mice, Inbred C57BL, Neoplasms, Phosphorylation, T-Lymphocytes, CD28 Antigens, Jurkat Cells, Mice, B7-H1 Antigen, Programmed Cell Death 1 Receptor
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