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Combination cancer immunotherapies tailored to the tumour microenvironment
Abstract
Evidence suggests that cancer immunotherapy will be a major part of the combination treatment plan for many patients with many cancer types in the near future. There are many types of immune processes involving different antitumour and tumour-promoting leucocytes, and tumour cells use many strategies to evade the immune response. The tumour microenvironment can help determine which immune suppressive pathways become activated to restrain antitumour immunity. This includes immune checkpoint receptors on effector T-cells and myeloid cells, and release of inhibitory cytokines and metabolites. Therapeutic approaches that target these pathways, particularly immune-checkpoint receptors, can induce durable antitumour responses in patients with advanced-stage cancers, including melanoma. Nevertheless, many patients do not have a good response to monotherapy approaches and alternative strategies are required to achieve optimal therapeutic benefit. These strategies include eliminating the bulk of tumour cells to provoke tumour-antigen release and antigen-presenting cell (APC) function, using adjuvants to enhance APC function, and using agents that enhance effector-cell activity. In this Review, we discuss the stratification of the tumour microenvironment according to tumour-infiltrating lymphocytes and PD-L1 expression in the tumour, and how this stratification enables the design of optimal combination cancer therapies tailored to target different tumour microenvironments.
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“On the other hand, some positive factors such as immunogenic cancer cell death, immunosupportive cytokines, and professional antigen presentation cells (pAPCs) contribute to immune clearance [21].”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [21]
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“By contrast, atezolizumab, avelumab, durvalumab, nivolumab and pembrolizumab are representative immune checkpoint inhibitors that are approved for the treatment of patients with certain types of cancer (34,68).”
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Metadata
- Authors
- Smyth, M. J., Ngiow, S. F., Ribas, A., & Teng, M. W. L.
- Affiliations
- QIMR Berghofer Medical Research Institute (AU)
- University of California, Los Angeles (US)
- Corresponding author
- Teng, Michele W. L.
- Venue
- Nature Reviews Clinical Oncology
- Published
- 2015-11-24
- Volume
- 13
- Issue
- 3
- Pages
- 143-158
- ISSN
- 1759-4774 (ISSN-L)
- 1759-4782
- OpenAlex
- W2257916459
- Cited by
- 944
- References
- 218
- Citations by year
- 2026: 28 · 2025: 50 · 2024: 71 · 2023: 82 · 2022: 132 · 2021: 102 · 2020: 134 · 2019: 95 · 2018: 99 · 2017: 89 · 2016: 56 · 2015: 3
- FWCI
- 8.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Amgen
- Bristol-Myers Squibb
- Kite Pharma
- National Cancer Institute (R35CA197633)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- cancer immunotherapy, combination therapy, tumor microenvironment, immune evasion, immune checkpoint receptors, PD-L1, tumor-infiltrating lymphocytes, myeloid cells, inhibitory cytokines, antigen-presenting cells, adjuvants, melanoma
- MeSH terms
- Adjuvants, Immunologic, Animals, Antibodies, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Humans, Immunotherapy, Neoplasms, Signal Transduction, Treatment Outcome, Tumor Escape, Molecular Targeted Therapy, Tumor Microenvironment, B7-H1 Antigen
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