Novel immune checkpoint targets: moving beyond PD-1 and CTLA-4
Open accessAbstract
The emergence of immune checkpoint inhibitors (ICIs), mainly including anti-programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) and anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) monoclonal antibodies (mAbs), has shaped therapeutic landscape of some type of cancers. Despite some ICIs have manifested compelling clinical effectiveness in certain tumor types, the majority of patients still showed de novo or adaptive resistance. At present, the overall efficiency of immune checkpoint therapy remains unsatisfactory. Exploring additional immune checkpoint molecules is a hot research topic. Recent studies have identified several new immune checkpoint targets, like lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin and mucin-domain containing-3 (TIM-3), T cell immunoglobulin and ITIM domain (TIGIT), V-domain Ig suppressor of T cell activation (VISTA), and so on. The investigations about these molecules have generated promising results in preclinical studies and/or clinical trials. In this review, we discussed the structure and expression of these newly-characterized immune checkpoints molecules, presented the current progress and understanding of them. Moreover, we summarized the clinical data pertinent to these recent immune checkpoint molecules as well as their application prospects.
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Blockade of a single immune checkpoint may lead to compensatory upregulation of other checkpoint receptors in the tumour microenvironment.
“These experiments indicated that the blockade of a single immune checkpoint may lead to compensatory upregulation of other checkpoint receptors in TME [30].”
From Immune Checkpoint Inhibitors in Cancer Therapy (2022) · cites this paper as [30]
Other immune checkpoints, abnormal angiogenesis, immunosuppressive immune cells or cytokines, cancer-associated adipocytes, and hyperactive cancer-associated fibroblasts also modulate the cancer-immune set point and promote immune tolerance.
“Apart from PD-1 signaling, other immune checkpoints, abnormal angiogenesis, immunosuppressive immune cells or cytokines, cancer-associated adipocytes, and hyperactive cancer-associated fibroblasts also modulate cancer-immune set point and promote immune tolerance [15–20].”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [15]
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- Authors
- Qin, S., Xu, L., Yi, M., Yu, S., Wu, K., & Luo, S.
- Affiliations
- Tongji Hospital (CN)
- Zhengzhou University (CN)
- Corresponding author
- Wu, Kongming
- Luo, Suxia
- Venue
- Molecular Cancer
- Published
- 2019-11-06
- Volume
- 18
- Issue
- 1
- Pages
- 155-155
- ISSN
- 1476-4598 (ISSN-L)
- PMC
- PMC6833286
- OpenAlex
- W2987385271
- Cited by
- 1,145
- References
- 129
- Citations by year
- 2026: 68 · 2025: 132 · 2024: 192 · 2023: 198 · 2022: 232 · 2021: 235 · 2020: 86 · 2013: 1
- FWCI
- 13.21
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Molecular Cancer (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (81572608, 81874120)
- Wuhan Municipal Science and Technology Bureau (2017060201010170)
- 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 inhibitors, immune checkpoint targets, PD-1/PD-L1, CTLA-4, LAG-3, TIM-3, TIGIT, VISTA, cancer immunotherapy, immune resistance, monoclonal antibodies
- MeSH terms
- Antineoplastic Agents, Immunological, Animals, Clinical Trials as Topic, Humans, Lymphocyte Activation, Neoplasms, T-Lymphocytes, Biomarkers, Tumor, Treatment Outcome, Immunomodulation, Molecular Targeted Therapy, CTLA-4 Antigen, Programmed Cell Death 1 Receptor
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