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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Additional file 16 of Single-cell RNA-seq reveals the genesis and heterogeneity of tumor microenvironment in pancreatic undifferentiated carcinoma with osteoclast-like giant-cells
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Additional file 15 of Single-cell RNA-seq reveals the genesis and heterogeneity of tumor microenvironment in pancreatic undifferentiated carcinoma with osteoclast-like giant-cells
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Additional file 23 of Single-cell RNA-seq reveals the genesis and heterogeneity of tumor microenvironment in pancreatic undifferentiated carcinoma with osteoclast-like giant-cells
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Additional file 12 of Single-cell RNA-seq reveals the genesis and heterogeneity of tumor microenvironment in pancreatic undifferentiated carcinoma with osteoclast-like giant-cells
Wang, X., Miao, J., Wang, S., Shen, R., Zhang, S., Tian, Y., Li, M., Zhu, D., Yao, A., Bao, W., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20130914
Additional file 11 of Single-cell RNA-seq reveals the genesis and heterogeneity of tumor microenvironment in pancreatic undifferentiated carcinoma with osteoclast-like giant-cells
Wang, X., Miao, J., Wang, S., Shen, R., Zhang, S., Tian, Y., Li, M., Zhu, D., Yao, A., Bao, W., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20130911
Additional file 13 of Single-cell RNA-seq reveals the genesis and heterogeneity of tumor microenvironment in pancreatic undifferentiated carcinoma with osteoclast-like giant-cells
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Additional file 24 of Single-cell RNA-seq reveals the genesis and heterogeneity of tumor microenvironment in pancreatic undifferentiated carcinoma with osteoclast-like giant-cells
Wang, X., Miao, J., Wang, S., Shen, R., Zhang, S., Tian, Y., Li, M., Zhu, D., Yao, A., Bao, W., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20130953
Additional file 18 of Single-cell RNA-seq reveals the genesis and heterogeneity of tumor microenvironment in pancreatic undifferentiated carcinoma with osteoclast-like giant-cells
Wang, X., Miao, J., Wang, S., Shen, R., Zhang, S., Tian, Y., Li, M., Zhu, D., Yao, A., Bao, W., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20130932
Additional file 21 of Single-cell RNA-seq reveals the genesis and heterogeneity of tumor microenvironment in pancreatic undifferentiated carcinoma with osteoclast-like giant-cells
Wang, X., Miao, J., Wang, S., Shen, R., Zhang, S., Tian, Y., Li, M., Zhu, D., Yao, A., Bao, W., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20130944
Additional file 14 of Single-cell RNA-seq reveals the genesis and heterogeneity of tumor microenvironment in pancreatic undifferentiated carcinoma with osteoclast-like giant-cells
Wang, X., Miao, J., Wang, S., Shen, R., Zhang, S., Tian, Y., Li, M., Zhu, D., Yao, A., Bao, W., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20130920
Additional file 2 of Combine and conquer: manganese synergizing anti-TGF-β/PD-L1 bispecific antibody YM101 to overcome immunotherapy resistance in non-inflamed cancers
Yi, M., Niu, M., Zhang, J., Li, S., Zhu, S., Yan, Y., Li, N., Zhou, P., Chu, Q., & Wu, K. (2021) · Figshare · doi:10.6084/m9.figshare.16625386
Additional file 22 of Single-cell RNA-seq reveals the genesis and heterogeneity of tumor microenvironment in pancreatic undifferentiated carcinoma with osteoclast-like giant-cells
Wang, X., Miao, J., Wang, S., Shen, R., Zhang, S., Tian, Y., Li, M., Zhu, D., Yao, A., Bao, W., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20130947
Additional file 20 of Single-cell RNA-seq reveals the genesis and heterogeneity of tumor microenvironment in pancreatic undifferentiated carcinoma with osteoclast-like giant-cells
Wang, X., Miao, J., Wang, S., Shen, R., Zhang, S., Tian, Y., Li, M., Zhu, D., Yao, A., Bao, W., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20130941
Additional file 26 of Single-cell RNA-seq reveals the genesis and heterogeneity of tumor microenvironment in pancreatic undifferentiated carcinoma with osteoclast-like giant-cells
Wang, X., Miao, J., Wang, S., Shen, R., Zhang, S., Tian, Y., Li, M., Zhu, D., Yao, A., Bao, W., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20130959
Additional file 25 of Single-cell RNA-seq reveals the genesis and heterogeneity of tumor microenvironment in pancreatic undifferentiated carcinoma with osteoclast-like giant-cells
Wang, X., Miao, J., Wang, S., Shen, R., Zhang, S., Tian, Y., Li, M., Zhu, D., Yao, A., Bao, W., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20130956
Additional file 17 of Single-cell RNA-seq reveals the genesis and heterogeneity of tumor microenvironment in pancreatic undifferentiated carcinoma with osteoclast-like giant-cells
Wang, X., Miao, J., Wang, S., Shen, R., Zhang, S., Tian, Y., Li, M., Zhu, D., Yao, A., Bao, W., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20130929
Additional file 10 of Single-cell RNA-seq reveals the genesis and heterogeneity of tumor microenvironment in pancreatic undifferentiated carcinoma with osteoclast-like giant-cells
Wang, X., Miao, J., Wang, S., Shen, R., Zhang, S., Tian, Y., Li, M., Zhu, D., Yao, A., Bao, W., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20130908
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Additional file 1 of Single-cell RNA-seq reveals the genesis and heterogeneity of tumor microenvironment in pancreatic undifferentiated carcinoma with osteoclast-like giant-cells
Wang, X., Miao, J., Wang, S., Shen, R., Zhang, S., Tian, Y., Li, M., Zhu, D., Yao, A., Bao, W., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20130938
Additional file 2 of Single-cell RNA-seq reveals the genesis and heterogeneity of tumor microenvironment in pancreatic undifferentiated carcinoma with osteoclast-like giant-cells
Wang, X., Miao, J., Wang, S., Shen, R., Zhang, S., Tian, Y., Li, M., Zhu, D., Yao, A., Bao, W., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20130962

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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