Cited by 663Cancer Immunotherapy and BiomarkersImmunotherapy and Immune ResponsesT-cell and B-cell Immunology

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Combination strategies to maximize the benefits of cancer immunotherapy

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Zhu, Shaoming, Zhang, Tian, Zheng, Lei, Liu, Hongtao, Song, Wenru, Liu, Delong, Li, Zihai, Pan, Chong-xian·2021·Journal of Hematology & Oncology

DOI 10.1186/s13045-021-01164-5PMC PMC8475356

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Abstract

Immunotherapies such as immune checkpoint blockade (ICB) and adoptive cell therapy (ACT) have revolutionized cancer treatment, especially in patients whose disease was otherwise considered incurable. However, primary and secondary resistance to single agent immunotherapy often results in treatment failure, and only a minority of patients experience long-term benefits. This review article will discuss the relationship between cancer immune response and mechanisms of resistance to immunotherapy. It will also provide a comprehensive review on the latest clinical status of combination therapies (e.g., immunotherapy with chemotherapy, radiation therapy and targeted therapy), and discuss combination therapies approved by the US Food and Drug Administration. It will provide an overview of therapies targeting cytokines and other soluble immunoregulatory factors, ACT, virotherapy, innate immune modifiers and cancer vaccines, as well as combination therapies that exploit alternative immune targets and other therapeutic modalities. Finally, this review will include the stimulating insights from the 2020 China Immuno-Oncology Workshop co-organized by the Chinese American Hematologist and Oncologist Network (CAHON), the China National Medical Product Administration (NMPA) and Tsinghua University School of Medicine.

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Fig. 1 Timeline of the FDA approvals of combination therapyCC BY · PubMed Central

Fig. 2 The cancer-immunity cycle, resistant mechanisms and potential solutionsCC BY · PubMed Central

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Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1-selective pressure in T lymphocytes
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VISTA is an inhibitory immune checkpoint that is increased after ipilimumab therapy in patients with prostate cancer
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Shalabi H, Shah NN, Fry TJ, Yates B, Delbrook C, Yuan C, Stetler-Stevenson M, Ramakrishna S. Intensification of lymphodepletion optimizes CAR re-treatment efficacy. Blood. 2017;130(Supplement 1):3889–3889.

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Authors: Zhu, S., Zhang, T., Zheng, L., Liu, H., Song, W., Liu, D., Li, Z., & Pan, C.-X.
Affiliations: Beijing Chao-Yang Hospital, Capital Medical University (CN)
Duke University (US)
Johns Hopkins University (US)
University of Chicago (US)
New York Medical College (US)
The Ohio State University (US)
Harvard University (US)
Corresponding author: Li, Zihai
Pan, Chong-xian
ORCID: Zhu, Shaoming
Zhang, Tian
Zheng, Lei
Liu, Hongtao
Liu, Delong
Li, Zihai
Pan, Chong-xian
Venue: Journal of Hematology & Oncology
Publisher: Springer Science and Business Media LLC
Published: 2021-09-27
Volume: 14
Issue: 1
Pages: 156-156
ISSN: 1756-8722 (ISSN-L)
DOI: 10.1186/s13045-021-01164-5
PMC: PMC8475356
OpenAlex: W3202901824
Cited by: 654
References: 318
Citations by year: 2026: 78 · 2025: 163 · 2024: 206 · 2023: 127 · 2022: 77 · 2021: 2
FWCI: 12.51
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0 (tdm)
creativecommons.org/licenses/by/4.0 (vor)
Locations: Journal of Hematology & Oncology (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, other-oa)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Touro Scholar (Touro College) (submittedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: Tsinghua University
National Cancer Institute (P50CA062924)
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, immune checkpoint blockade, adoptive immunotherapy, immunotherapy resistance, cancer vaccines, virotherapy, cytokine-targeted therapy, combination chemotherapy, radiation therapy combination, combination targeted therapy
MeSH terms: Immune Checkpoint Inhibitors, Animals, Combined Modality Therapy, Humans, Immunotherapy, Neoplasms, Cancer Vaccines, Oncolytic Virotherapy

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Combination strategies to maximize the benefits of cancer immunotherapy

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