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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Kurtuluş, S., Sakuishi, K., Ngiow, S. F., Joller, N., Tan, D. J., Teng, M. W. L., Smyth, M. J., Kuchroo, V. K., & Anderson, A. C. (2015) · Journal of Clinical Investigation · doi:10.1172/jci81187 · Cited by 558
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Knight, D. A., Ngiow, S. F., Li, M., Parmenter, T. J., Mok, S., Cass, A. A., Haynes, N. M., Kinross, K. M., Yagita∥, H., Koya, R. C., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci66236 · Cited by 274
Self-citation
Retracted
Stimulation of natural killer cells with a CD137-specific antibody enhances trastuzumab efficacy in xenotransplant models of breast cancer
Kohrt, H. E. K., Houot, R., Weiskopf, K., Goldstein, M. J., Scheeren, F. A., Czerwinski, D. K., Colevas, A. D., Weng, W., Clarke, M. F., Carlson, R. W., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci61226 · Cited by 226
Retracted
CD137 stimulation enhances the antilymphoma activity of anti-CD20 antibodies
Kohrt, H. E. K., Houot, R., Goldstein, M. J., Weiskopf, K., Alizadeh, A. A., Brody, J., Müller, A. M. S., Pachynski, R. K., Czerwinski, D. K., Coutre, S. E., et al. (2010) · Blood · doi:10.1182/blood-2010-08-301945 · Cited by 205
Retracted
Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989
Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review
Wanchoo, R., Karam, S., Uppal, N. N., Barta, V. S., Deray, G., Devoe, C., Launay‐Vacher, V., Jhaveri, K. D., & on behalf of Cancer and Kidney International Network Workgroup on Immune Checkpoint Inhibitors (2017) · American Journal of Nephrology · doi:10.1159/000455014 · Cited by 15,320
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma
Hodi, F. S., O'Day, S. J., McDermott, D. F., Weber, R. W., Sosman, J. A., Haanen, J. B., Gonzalez, R., Robert, C., Schadendorf, D., Hassel, J. C., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1003466 · Cited by 15,155
The blockade of immune checkpoints in cancer immunotherapy
Pardoll, D. M. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3239 · Cited by 13,838
Safety, activity, and immune correlates of anti–PD-1 antibody in cancer
Topalian, S. L., Hodi, F. S., Brahmer, J. R., Gettinger, S. N., Smith, D. C., McDermott, D. F., Powderly, J. D., Carvajal, R. D., Sosman, J. A., Atkins, M. B., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200690 · Cited by 12,628

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Hydrogel-Nanoparticle Bioactive Platforms for Post-Surgical Prevention of Tumor Recurrence
Măciuceanu-Zărnescu, B. M., Mușat, D. N., Niculescu, A.-G., Scafa‐Udriște, A., Grumezescu, A. M., Vâlcea, S., & Anghel, D. N. (2026) · Nanomaterials · doi:10.3390/nano16150924 · Cited by 3
“…local delivery of checkpoint inhibitors, TLR agonists, and pro-inflammatory cytokines, with evidence of systemic anti-tumor immune activation extending beyond the resection site, transforms locally acting platforms from pure drug-delivery devices into initiators of systemic immune responses [133].”
Improving Anti-cancer Immunotherapy by Simultaneous Targeting Suppressive Tumor Microenvironment
Bialkowski, L., & Thielemans, K. (2016) · Journal of Vaccines & Vaccination · doi:10.4172/2157-7560.1000324 · Cited by 3
“Therefore, acknowledging the influence of TME on the therapeutic response, the idea of a TME-tailored immunotherapy has been brought up in recent years [9,10].”
Background
Case report: Two PD-L1 positive unresectable advanced pancreatic carcinoma patients with microsatellite stability achieved R0 resection after PD-1 antibody plus chemotherapy as a successful downstaging therapy: A report of two cases
Shang, L., Li, P., Fan, J., Zhao, C., Niu, X., Bian, Q.-T., Yuan, Z., Kong, Y., Zhu, T., Xu, B., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.946266 · Cited by 3
“Frontiers in Immunology 04 achieving a partial response through chemotherapy alone (9).”
Background
Nivolumab as Second-Line Therapy Improves Survival in Patients with Unresectable Hepatocellular Carcinoma
Sanai, F. M., Odah, H., Alshammari, K. M., Alzanbagi, A., Alsubhi, M., Tamim, H., Alolayan, A. A. M., Alshehri, A., & Alqahtani, S. A. (2024) · Cancers · doi:10.3390/cancers16122196 · Cited by 3
“Monoclonal antibodies against programmed cell death protein 1 (PD-1) or its ligand 1 (PD-L1) have recently become standard-of-care for some cancers, such as non-small cell lung cancer, melanoma, and others [12].”
Background
The Tumor Microenvironment and Tumor-infiltrating Lymphocytes in Solid Tumor: A Comprehensive Review
Sun, Z., Qiu, L., Zhao, X. H., & Jiao, S.-C. (2024) · Oncology Advances · doi:10.14218/ona.2023.00043 · Cited by 3
“83 Teng et al . introduced a classification of the TME into four types based on the presence of TILs and PD-L1 expression, 84 aiding in predicting the tumor’s response to therapies targeting PD-1/PD-L1 pathways and serving as a valuable prognostic tool.”
Immune Checkpoint Inhibitors in Triple Negative Breast Cancer: What is the Evidence?
Chok, N., & Chokr, S. (2018) · Journal of Neoplasm · doi:10.21767/2576-3903.100031 · Cited by 3
Tumor-infiltrating OX40+ lymphocytes is an independent positive prognostic factor for patients with pancreatic ductal adenocarcinoma
Zhang, Q., Rui, W., Jiang, Y., Yuan, F., Chen, Y., Guo, X., Zhou, Y., Wu, Z., Wang, C., & Ding, X. (2022) · Clinical & Translational Oncology · doi:10.1007/s12094-022-02864-1 · Cited by 3
Role of Lymphocytes in Cancer Immunity and Immune Evasion Mechanisms
Kushekhar, K., Chellappa, S., Aandahl, E. M., & Taskén, K. (2022) · Springer eBooks · doi:10.1007/978-3-030-98950-7_10 · Cited by 6
Comprehensive Characterization of Immune Landscape Based on Tumor Microenvironment for Oral Squamous Cell Carcinoma Prognosis
Li, Q., Mao, J., & Meng, X. (2022) · Vaccines · doi:10.3390/vaccines10091521 · Cited by 3
“Therefore, a deeper understanding of the cell components (including immune cells and stromal cells) and the immunosuppressive status of the TME is critical for improving the efficacy of immunotherapy [18].”
Background
Identification and validation of an anoikis-related lncRNA signature to predict prognosis and immune landscape in osteosarcoma
Zhang, J., Pan, R., & Tian, X. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1156663 · Cited by 3
“The tumor microenvironment, which played a significant role in the treatment of OS, was identified as one of the most critical factors affecting immunotherapy (44, 45).”
Background
Some synergetic therapy strategies for overcoming hypoxia for photodynamic therapy of cancer
Chai, T., Li, Y., Cai, Y., Li, Y., Kenar, N., Lim, H. S., Temple, H., Chen, X., & Chen, W. (2023) · Journal of Cancer Metastasis and Treatment · doi:10.20517/2394-4722.2023.38 · Cited by 3
Integrated bioinformatics and validation reveal SOX12 as potential biomarker in colon adenocarcinoma based on an immune infiltration-related ceRNA network
Chen, X., Yang, M., Tu, J., & Yuan, X. (2023) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-023-05316-7 · Cited by 3
“It is also well-known that there is a complex network of interactions in the tumor microenvironment containing tumor-infiltrating immune cells, and more importantly, the characteristics of immune infiltration have a profound impact on the occurrence and development of tumors (Smyth et al. 2016).”
Background
Constructing a Novel Amino Acid Metabolism Signature: A New Perspective on Pheochromocytoma Diagnosis, Immune Landscape, and Immunotherapy
Yan, Z., Luan, Y., Wang, Y., Ren, Y., Li, Z., Zhao, L., Shen, L., Yang, X., Liu, T., Gao, Y., et al. (2024) · Biochemical Genetics · doi:10.1007/s10528-024-10733-5 · Cited by 3
“Interestingly, MDSC and Treg cell expression were elevated in low-risk patients with high antitumor activity, which may be attributed to TME containing a large number of immunosuppressive factors that greatly inhibit the antitumor function of immune cells.”
Influential
Multiple Expressed Endogenous Glioma Epitopes as Novel Vaccines for Gliomas
Lowenstein, P. R., & Castro, M. G. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-1477 · Cited by 3
“Inhibitors of costimulating molecule pairs CTLA4–CD28 and PD1–PDL1 have shown strong antitumoral activities across disease stages, even after failure of standard of care and various stages of disease progression (2, 3).”
Background
Engineering nanobiomaterials for cancer immunotherapy
Qin, F. A. N., & Wang, C. (2020) · Scientia Sinica Vitae · doi:10.1360/ssv-2019-0215 · Cited by 3
Immuno-genomic PanCancer Landscape Reveals Diverse Immune Escape Mechanisms and Immuno-Editing HistoriesPreprint
Mizuno, S., Yamaguchi, R., Hasegawa, T., Hayashi, S., Fujita, M., Zhang, F., Koh, Y., Lee, S., Yoon, S., Shimizu, E., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/285338 · Cited by 3
Inflammatory biomarkers as predictors of immune activation to different irradiated sites and short-term efficacy in advanced squamous cell esophageal carcinoma received radioimmunotherapy
Li, M., Cai, G., Gao, Z., Meng, X., & Han, X. W. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1117648 · Cited by 2
Remote‐Controllable Immune‐Priming Spot Formation Via Nanocomplexed Hydrogel‐Assisted Histotripsy: Immunoasis
Kim, S. H., Choi, W., Kim, Y. G., Kim, H., Jeong, G. S., Park, H., Youn, I., Park, Y., Han, S., & Kim, Y. (2025) · Advanced Materials · doi:10.1002/adma.202518245 · Cited by 2
Introducing, OncoTarget
Blagosklonny, M. V., & Gudkov, A. V. (2010) · Oncotarget · doi:10.18632/oncotarget.23444 · Cited by 2
Charakterisierung des Tumormikromilieus mittels Hochmultiplexmikroskopieverfahren
Schürch, C. M. (2022) · Die Pathologie · doi:10.1007/s00292-022-01129-6 · Cited by 2
(E)‐SIS3 suppressed osteosarcoma progression via promoting cell apoptosis, arresting cell cycle, and regulating the tumor immune microenvironment
Huang, Z. Y., Zhang, C., Zhu, K., Hu, J., Xu, E., Ma, X., Wang, Y., Zhu, Y., & Zhu, J. (2023) · Drug Development Research · doi:10.1002/ddr.22120 · Cited by 2
Prognostic signature and immune efficacy of m1A-, m5C-, m6A-, m7G-, and DNA methylation-related regulators in hepatocellular carcinoma
Liu, D., Zhou, X., & Zhao, J. (2024) · Journal of Cancer · doi:10.7150/jca.95730 · Cited by 2
“The tumor microenvironment (TME) plays a critical role in malignancy evolvement and immune regulation [47].”
Background
NSDHL promotes the degradation of sting in cholangiocarcinoma
Yu, W., Chen, J., Tong, Y., Zhu, L., Deng, Y., He, J., Zhong, C., & Cai, X. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e37592 · Cited by 2
“There is a dearth of studies on metabolic enzymes that directly impact immune regulation [18].”
Background
A bibliometric analysis of oncolytic virotherapy combined with immunotherapy
Zhang, T., Jiang, S., Zhang, L., Liu, Y., Han, Z., Zhao, H., Du, S., Xu, Y., & Lu, X. (2024) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2024.2406621 · Cited by 2
“32,33 In the top 20 keywords with the strongest citation bursts, ‘tumor microenvironment’ and ‘delivery’ were keywords that continued to burst as of 2023.”
Background
Case report: a case of R0 resection in a patient with PD-L1-negative, microsatellite-stabilized advanced pancreatic cancer after down-stage treatment with a PD-1 inhibitor in combination with chemotherapy
Dang, J., Wang, Q., Yang, Y., Shang, L., Kang, Z., Jiang, Y., Ren, Y., & Xiang, H. (2025) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-025-06147-4 · Cited by 2
“…NAT in patients with UR-PDAC and have achieved a certain degree of efficacy, the abundance of interstitial stroma in pancreatic cancers makes it difficult for chemotherapeutic agents to penetrate, resulting in patients seldom achieving partial remission with chemotherapy alone (Smyth et al. 2016).”
Cancer Resistance to Immunotherapy
Khoury, R., Shayya, A., Orm, C. B., Deen, O. Z., & Ghanem, H. (2025) · Immuno · doi:10.3390/immuno5030032 · Cited by 2
“Higher tumor mutational burdens are substantially correlated with response to both anti-CTLA-4 and anti-PD-1 across many cancer indications [40,41].”
Immunology and Immunotherapy of Colorectal Cancer
Varela‐Calviño, R., & Cordero, O. J. (2015) · Springer eBooks · doi:10.1007/978-3-662-46410-6_11 · Cited by 2
Challenges of Immunotherapy
Rotte, A., & Bhandaru, M. (2016) · Springer eBooks · doi:10.1007/978-3-319-48066-4_16 · Cited by 2
Immune Checkpoint Blockade and Gastric Cancer
Su, S., & Liu, B. (2017) · Springer eBooks · doi:10.1007/978-981-10-3978-2_9 · Cited by 2
Nivolumab Enhances the Inflammation of the Irradiation Field in Advanced Non–Small Cell Lung Cancer
Furuta, H., Yoshida, T., Shimizu, J., Tomita, N., Yatabe, Y., & Hida, T. (2017) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2017.07.025 · Cited by 2
“Thus, the results of the combined use of nivolumab and radiation therapy (RT), standard chemotherapy, molecular target agents, or other immune checkpoint inhibitors are highly anticipated.(5)”
Background
A Cpg Fever For Cancer Nanovaccine
Zhang, H., & Xia, X. (2018) · Immunotherapy · doi:10.2217/imt-2018-0052 · Cited by 2
[New Progress in the Relationship between Immune Cells, PD-1 in Tumor Microenvironment and the Efficacy of EGFR-TKIs].
Yuan, S., Xu, H. M., & Xie, J. (2017) · Europe PMC (PubMed Central) · doi:10.3779/j.issn.1009-3419.2017.11.09 · Cited by 2
Concluding remarks and future perspective of combination drug delivery systems
Nasser, T. A., AbdElhamid, A. S., Teleb, M., Khattab, S. N., Bekhit, A. A., Elkhodairy, K. A., & Elzoghby, A. O. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-85873-1.00004-6 · Cited by 2
Systematic Analysis of Molecular Subtypes and Immune Prediction Based on CD8 T Cell Pattern Genes Based on Head and Neck Cancer
Li, Y., He, F., Liu, S., & Pan, Z. (2022) · Journal of Oncology · doi:10.1155/2022/1500493 · Cited by 2
“TILs play a vital role in tumour formation, growth, invasion, and metastasis and have predictive prognostic value [9, 10].”
Background
Positive regulators of T cell proliferation as biomarkers for predicting prognosis and characterizing the immune landscape in lung adenocarcinoma
Li, Y., Peng, G., Qin, C., Wang, X., Li, Y., & Li, Y. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.1003754 · Cited by 2
“We attributed this result to the optimal localization andmigration of T cells, which is essential for immune surveillance and the inhibition of tumor initiation (Smyth et al., 2016).”
Background
Tumor immunology
Sharif, P. M., Khoshbin, A. P., Nasrollahzadeh, E., Keshavarz‐Fathi, M., & Rezaei, N. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-818006-8.00003-7 · Cited by 3
Identification and validation of a cancer-associated fibroblasts-related scoring system to predict prognosis and immune landscape in hepatocellular carcinoma through integrated analysis of single-cell and bulk RNA-sequencing
Bao, L., Zhang, X., Wang, W., & Jiang, B. (2023) · Aging · doi:10.18632/aging.205099 · Cited by 2
Blockade of CD73 Increases the Cytotoxic Effects of Fludarabine in Chronic Lymphocytic Leukemia
Sadeghi, M. R. T., Bostanabad, M. Y., Abedi, O., Feizi, A. A. H., Akbari, A. A. M., & Jadidi‐Niaragh, F. (2022) · ImmunoAnalysis · doi:10.34172/ia.2022.11 · Cited by 2
Multiplex immunohistochemistry/immunofluorescence is superior to tumor mutational burden and PD‐L1 immunohistochemistry for predicting response to anti‐PD‐1/PD‐L1 immunotherapy
Hu, W. (2019) · Thoracic Cancer · doi:10.1111/1759-7714.13233 · Cited by 2
Deconvolving clinically relevant cellular immune crosstalk from bulk gene expression using CODEFACS and LIRICSPreprint
Wang, K., Patkar, S., Lee, J. S., Gertz, E. M., Robinson, W., Schischlik, F., Crawford, D. R., Schäffer, A. A., & Ruppin, E. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.01.20.427515 · Cited by 2
Harnessing the Immune System to Target Cancer Cells
Maccalli, C. (2019) · Resistance to targeted anti-cancer therapeutics · doi:10.1007/978-3-030-16624-3_6 · Cited by 1
Membrane (CD8⁺PD-1⁺ and CD4+PD-1⁺) and soluble (sPD-1 and sPD-L1) forms of immune checkpoints in melanoma, breast cancer, and oral mucosal cancer patients: A observational study
Заботина, Т. Н., Ивановна, Ч. А., Анатольевна, Б. А., Кушлинский, Н. Е., Герштейн, Е. С., Захарова, Е. Н., Константиновна, Ш. Э., Тамазиевич, Ц. В., Самойленко, И. В., Khoroshilov, M. V., et al. (2023) · Journal of Modern Oncology · doi:10.26442/18151434.2023.3.202443 · Cited by 1

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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