Clinical Application of Cytokines in Cancer Immunotherapy

Abstract

Cytokines are key components of the immune system and play pivotal roles in anticancer immune response. Cytokines as either therapeutic agents or targets hold clinical promise for cancer precise treatment. Here, we provide an overview of the various roles of cytokines in the cancer immunity cycle, with a particular focus on the clinical researches of cytokine-based drugs in cancer therapy. We review 27 cytokines in 2630 cancer clinical trials registered with ClinicalTrials.gov that had completed recruitment up to January 2021 while summarizing important cases for each cytokine. We also discuss recent progress in methods for improving the delivery efficiency, stability, biocompatibility, and availability of cytokines in therapeutic applications.

Keywords:

• cytokine therapy
• cancer immunity cycle
• cancer immunotherapy
• clinical trial
• nanomedicine

Acknowledgments

This work is supported by the National Natural Science Foundation of China (Grant No. 31800006) to YQ; Natural Science Foundation of Guangdong Province (Grant No. 18zxxt26) to YQ; Guangzhou Basic and Applied Basic Research Foundation (Grant No. 202002030127) to JS; Guangdong Basic and Applied Basic Research Foundation (Grant No. 2021A1515012324) to JS; the Fundamental Research Funds for the Central Universities (Grant No. 20ykzd08) to JS; Natural Science Foundation of Guangdong Province (Grant No. 2018A030313563) to JS; Program for Guangdong Introducing Innovative and Entrepreneurial Teams (Grant No. 2016ZT06S252) to JS; Guangdong Financial Fund for High-Caliber Hospital Construction to JS.

Abbreviations

APC, antigen-presenting cell; B7-H3, B7 homolog 3 protein; CAR-T, chimeric antigen receptor T cell; CCL, C-C motif chemokine ligand; CRC, colorectal cancer; CSF, colony-stimulating factor; CTL, cytotoxic T lymphocyte; CTLA-4, cytotoxic T lymphocyte-associated protein 4; CXCL, chemokine (C-X-C motif) ligand; DC, dendritic cell; EGF, epidermal growth factor; EMT, epithelial-to-mesenchymal transition; EPO, erythropoietin; FDA, US Food and Drug Administration; FGF, fibroblast growth factor; Fu, fluorouracil; G, granulocyte; GM, granulocyte/macrophage; IFN, interferon; IGF, insulin-like growth factor; IL, interleukin; ILC, innate lymphoid cell; i.v., intravenous injection; IU, international unit; JAK, Janus kinase; MDSC, myeloid-derived suppressor cell; MHC, major histocompatibility complex; mRCC, metastatic renal cell carcinoma; NK, natural killer; NKT, natural killer T; NSCLC, non-small-cell-lung cancer; ORR, objective response rate; OS, overall survival; PD-1, programmed death 1; PD-L1, programmed death ligand 1; PEG, pegylated; PFS, progression-free survival; PGE2, prostaglandin E2; PLGA, poly (lactic-co-glycolic acid); rAd, recombinant adenovirus; STAT, signal transducer and activator of transcription; s.c., subcutaneous injection. TAA, tumor-associated antigen; TAM, tumor-associated macrophage; TGF-β, transforming growth factor β; Th, T helper cell; TNF, tumor necrosis factor; Treg, regulatory T cell; VEGF, vascular endothelial growth factor; VEGFR, VEGF receptor.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare they have no competing financial interests and other onflicts of interest in this work.