Cited by 965Cancer Immunotherapy and BiomarkersImmunotherapy and Immune ResponsesT-cell and B-cell Immunology

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Combination cancer immunotherapies tailored to the tumour microenvironment

Smyth, Mark J., Ngiow, Shin Foong, Ribas, Antoni, Teng, Michele W. L.·2016·Nature Reviews Clinical Oncology

DOI 10.1038/nrclinonc.2015.209

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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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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.
ORCID: Smyth, Mark J.
Ngiow, Shin Foong
Ribas, Antoni
Teng, Michele W. L.
Venue: Nature Reviews Clinical Oncology
Publisher: Springer Science and Business Media LLC
Published: 2015-11-24
Volume: 13
Issue: 3
Pages: 143-158
ISSN: 1759-4774 (ISSN-L)
1759-4782
DOI: 10.1038/nrclinonc.2015.209
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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Combination cancer immunotherapies tailored to the tumour microenvironment

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