The DOI matches its Crossref record; 105 of the 105 references it cites were found in a registry or an index.
Reversing T-cell Dysfunction and Exhaustion in Cancer
Open accessAbstract
In the context of chronic antigen exposure in chronic viral infections and cancer, T cells become exhausted/dysfunctional. These exhausted T cells exhibit defective proliferative capacities and cytokine production, but are not totally inert and may exert lytic functions. Importantly, exhausted T cells upregulate multiple inhibitory receptors/immune checkpoints that bind to their ligands expressed by tumor cells and antigen-presenting cells in the tumor microenvironment (TME). Immune checkpoint blockades with anti-CTL antigen 4 (CTLA-4) and/or anti-programmed death 1 (PD-1) mAbs successfully reinvigorate tumor-infiltrating T lymphocytes and provide persistent clinical benefits to a large number of patients with advanced cancer. This great and long-awaited success for the immunotherapy of cancer has infused considerable enthusiasm in the field of oncology and fostered the development of combinatorial strategies to target the multiple mechanisms of tumor-induced T-cell dysfunction. Here, we review the critical immunoregulatory mechanisms driving T-cell exhaustion in the TME. We also discuss the development of promising combinatorial immunotherapies to counteract the mechanisms of tumor-induced T-cell dysfunction to improve the clinical efficacy of current immune checkpoint blockades. As our understanding of the mechanisms supporting tumor-induced T-cell dysfunction improves based upon preclinical and clinical studies, we expect that novel combinatorial immunotherapies will emerge to improve the clinical outcome of patients with advanced cancers. Clin Cancer Res; 22(8); 1856–64. ©2016 AACR. See all articles in this CCR Focus section, “Opportunities and Challenges in Cancer Immunotherapy.”
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“the gut microbiome is a major tumor-extrinsic regulator of responses to anti–PD-1 (6–9).”
From Fecal microbiota transplant overcomes resistance to anti–PD-1 therapy in melanoma patients (2021) · cites this paper as [9]
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1 retracted
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Fecal microbiota transplant overcomes resistance to anti–PD-1 therapy in melanoma patients
Davar, D., Dzutsev, A. K., McCulloch, J. A., Rodrigues, R. R., Chauvin, J.-M., Morrison, R. M., Deblasio, R. N., Menna, C., Ding, Q., Pagliano, O., et al. (2021) · Science · doi:10.1126/science.abf3363 · Cited by 1,781
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T Cell Dysfunction and Exhaustion in Cancer
Zhang, Z., Liu, S., Zhang, B., Qiao, L., Zhang, Y., & Zhang, Y. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00017 · Cited by 385
“Thus, a combined treatment of IL-10 or TGF-β inhibitor(s) with ICB represents a promising strategy for immunotherapy strategy (Zarour, 2016).”
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Immunological Mechanisms Underneath the Efficacy of Cancer Therapy
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Metadata
- Authors
- Zarour, H. M.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Zarour, Hassane M.
- ORCID
- Zarour, Hassane M.
- Venue
- Clinical Cancer Research
- Published
- 2016-04-14
- Volume
- 22
- Issue
- 8
- Pages
- 1856-1864
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC4872712
- OpenAlex
- W2336635113
- Cited by
- 462
- References
- 105
- Citations by year
- 2026: 29 · 2025: 42 · 2024: 35 · 2023: 55 · 2022: 59 · 2021: 64 · 2020: 53 · 2019: 46 · 2018: 38 · 2017: 25 · 2016: 15
- FWCI
- 4.16
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH Melanoma Research Alliance, and a Clinical Strategy Team Grant from the Cancer Research Institute (R01CA157467 and P50CA121973)
- 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
- T cell exhaustion, T cell dysfunction, tumor microenvironment, immune checkpoint, CTLA-4, PD-1, immune checkpoint blockade, cancer immunotherapy, combination immunotherapy, inhibitory receptors, chronic viral infection, tumor-infiltrating T cells
- MeSH terms
- Animals, Antibodies, Monoclonal, Antigen-Presenting Cells, Antineoplastic Agents, Gene Expression Regulation, Humans, Immunologic Factors, Neoplasms, T-Lymphocytes, Signal Transduction, Cytokines, Myeloid Cells, Epigenesis, Genetic, Immunomodulation, Molecular Targeted Therapy, Tumor Microenvironment, CTLA-4 Antigen, Costimulatory and Inhibitory T-Cell Receptors, Programmed Cell Death 1 Receptor
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