PD-1 blockade combined with IL-33 enhances the antitumor immune response in a type-1 lymphocyte-mediated manner

Honghong He; Liyan Shi; Dan Meng; Huijun Zhou; Jingshu Ma; Yixian Wu; Yanshi Wu; Yanzheng Gu; Wei Xie; Jing Zhang; Yibei Zhu

doi:10.1016/j.ctarc.2021.100379

PD-1 blockade combined with IL-33 enhances the antitumor immune response in a type-1 lymphocyte-mediated manner

Cancer Treat Res Commun. 2021:28:100379. doi: 10.1016/j.ctarc.2021.100379. Epub 2021 Apr 23.

Authors

Honghong He¹, Liyan Shi², Dan Meng³, Huijun Zhou⁴, Jingshu Ma⁴, Yixian Wu⁴, Yanshi Wu⁴, Yanzheng Gu⁵, Wei Xie⁴, Jing Zhang³, Yibei Zhu⁶

Affiliations

¹ Department of Immunology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China; Suzhou Blood Center, Suzhou 215006, China.
² Department of Immunology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China; Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou 215006, China.
³ Suzhou Junmeng Biopharm Co., Ltd, Suzhou 215200, China.
⁴ Department of Immunology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China.
⁵ Jiangsu Key Laboratory of Clinical Immunology, Soochow University, Suzhou 215006, China; Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
⁶ Department of Immunology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China; Jiangsu Key Laboratory of Clinical Immunology, Soochow University, Suzhou 215006, China; Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China. Electronic address: [email protected].

PMID: 33951555
DOI: 10.1016/j.ctarc.2021.100379

Abstract

PD-1 immune checkpoint blockade and cytokine IL-33 have shown significant therapeutic effects in tumor immunotherapy. These therapies promote CD8⁺ T cell activation, proliferation, and effector functions. However, there were few research about the combined therapy efficacy. In this study, we established B16-empty vector and B16-IL33 melanoma mouse models and treated with PD-1 monoclonal antibody. We reported that PD-1 blockade combined with cytokine IL-33 further inhibited tumor progression and prolonged the survival of tumor-bearing mice. Mechanistically, the combination therapy was found to further facilitate CD4⁺ and CD8⁺ T lymphocytes accumulation, and enhance the antitumor effects of CD4⁺or CD8⁺tumor-infiltrating lymphocytes by promoting type-1 immune response within the tumor microenvironment using flow cytometry and quantitative real time polymerase chain reaction. Thus, PD-1 blockade combined with IL-33 has application potential in tumor immunotherapy. Further, this study provides a new promising strategy and theoretical basis for tumor combination immunotherapy.

Keywords: IL-33; Immune checkpoint blockade; Melanoma; PD-1; Tumor immunotherapy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Monoclonal, Humanized / pharmacology
Antibodies, Monoclonal, Humanized / therapeutic use*
Antineoplastic Combined Chemotherapy Protocols / pharmacology
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
CD4-Positive T-Lymphocytes / drug effects
CD4-Positive T-Lymphocytes / immunology
CD8-Positive T-Lymphocytes / drug effects
CD8-Positive T-Lymphocytes / immunology
Cell Line, Tumor
Drug Synergism
Female
Immune Checkpoint Inhibitors / pharmacology
Immune Checkpoint Inhibitors / therapeutic use*
Immunotherapy
Interleukin-33 / pharmacology
Interleukin-33 / therapeutic use*
Lymphocytes, Tumor-Infiltrating / drug effects
Lymphocytes, Tumor-Infiltrating / immunology
Melanoma, Experimental / drug therapy*
Melanoma, Experimental / immunology
Melanoma, Experimental / pathology
Mice, Transgenic
Programmed Cell Death 1 Receptor / antagonists & inhibitors*
Skin Neoplasms / drug therapy*
Skin Neoplasms / immunology
Skin Neoplasms / pathology
Tumor Microenvironment / drug effects
Tumor Microenvironment / immunology

Substances

Antibodies, Monoclonal, Humanized
Immune Checkpoint Inhibitors
Interleukin-33
Pdcd1 protein, mouse
Programmed Cell Death 1 Receptor
toripalimab