The DOI matches its Crossref record; 226 of the 226 references it cites were found in a registry or an index.
Combinatorial blockade for cancer immunotherapy: targeting emerging immune checkpoint receptors
Open accessAbstract
The differentiation, survival, and effector function of tumor-specific CD8+ cytotoxic T cells lie at the center of antitumor immunity. Due to the lack of proper costimulation and the abundant immunosuppressive mechanisms, tumor-specific T cells show a lack of persistence and exhausted and dysfunctional phenotypes. Multiple coinhibitory receptors, such as PD-1, CTLA-4, VISTA, TIGIT, TIM-3, and LAG-3, contribute to dysfunctional CTLs and failed antitumor immunity. These coinhibitory receptors are collectively called immune checkpoint receptors (ICRs). Immune checkpoint inhibitors (ICIs) targeting these ICRs have become the cornerstone for cancer immunotherapy as they have established new clinical paradigms for an expanding range of previously untreatable cancers. Given the nonredundant yet convergent molecular pathways mediated by various ICRs, combinatorial immunotherapies are being tested to bring synergistic benefits to patients. In this review, we summarize the mechanisms of several emerging ICRs, including VISTA, TIGIT, TIM-3, and LAG-3, and the preclinical and clinical data supporting combinatorial strategies to improve existing ICI therapies.
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“Physiologically, CTLA-4 is an immune checkpoint receptor expressed on Foxp3+ regulatory T cells and conventional T cells.”
From Preclinical development of an mRNA-based multiepitope immunotherapeutic for glioblastoma (2025) · cites this paper as [44]
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“CTLA-4 has also been detected in natural killer cells, B cells, dendritic cells and myeloid cells [44].”
From Preclinical development of an mRNA-based multiepitope immunotherapeutic for glioblastoma (2025) · cites this paper as [44]
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Items 201–226 of 226
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Flagged first, then by citations
Research works printed but not linked: 1
- Huang, 2015, LAG3 and PD1 co-inhibitory molecules collaborate to limit CD8+ T cell signaling and dampen antitumor immunity in a murine ovarian cancer model, Oncotarget, 6, 10.18632/oncotarget.4751 · DOI
Cited by
Sorted by citations
Preclinical development of an mRNA-based multiepitope immunotherapeutic for glioblastoma
Lutz, J., Feist, R. K., Sonntag, T., Peguero-Sánchez, E., Wolter, K., Bick, R., Bauer, J., Walz, J. S., & Heidenreich, R. (2025) · Cancer Immunology, Immunotherapy · doi:10.1007/s00262-025-04178-x · Cited by 9
Metadata
- Authors
- Roy, D., Gilmour, C., Patnaik, S., & Wang, L. L.
- Affiliations
- Cleveland Clinic (US)
- Corresponding author
- Wang, Li Lily
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2023-10-19
- Volume
- 14
- Pages
- 1264327-1264327
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC10620683
- OpenAlex
- W4387777058
- Cited by
- 53
- References
- 226
- Citations by year
- 2026: 15 · 2025: 24 · 2024: 13 · 2023: 1
- FWCI
- 1.71
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Immunology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. Department of Defense (W81XWH)
- National Cancer Institute (R01CA223804, R21CA258618, R01CA164225, F31CA257276)
- Congressionally Directed Medical Research Programs (W81XWH-21-MRP-MCAA ME210229, W81XWH-21-LCRP-IITRA LC210336)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- immune checkpoint receptors, immune checkpoint inhibitors, combination immunotherapy, T cell exhaustion, PD-1, CTLA-4, VISTA, TIGIT, TIM-3, LAG-3, cytotoxic T lymphocytes, antitumor immunity, costimulation
- MeSH terms
- Hepatitis A Virus Cellular Receptor 2, Humans, Immunotherapy, Neoplasms, Receptors, Immunologic, T-Lymphocytes, Cytotoxic
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