Cancer immunotherapy with immune checkpoint inhibitors (ICIs): potential, mechanisms of resistance, and strategies for reinvigorating T cell responsiveness when resistance is acquired

Hany E Marei; Anwarul Hasan; Giacomo Pozzoli; Carlo Cenciarelli

doi:10.1186/s12935-023-02902-0

Cancer immunotherapy with immune checkpoint inhibitors (ICIs): potential, mechanisms of resistance, and strategies for reinvigorating T cell responsiveness when resistance is acquired

Cancer Cell Int. 2023 Apr 10;23(1):64. doi: 10.1186/s12935-023-02902-0.

Authors

Hany E Marei¹, Anwarul Hasan², Giacomo Pozzoli^{3

4}, Carlo Cenciarelli⁵

Affiliations

¹ Department of Cytology and Histology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, 35116, Egypt. hanymarei@mans.edu.eg.
² Department of Mechanical and Industrial Engineering, College of Engineering, Qatar University, Doha, Qatar.
³ Pharmacology Section, Department of Health Care Surveillance and Bioethics, Università Cattolica del Sacro Cuore, Rome, Italy.
⁴ Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
⁵ Institute of Translational Pharmacology-CNR, Rome, Italy.

Abstract

Cancer is still the leading cause of death globally. The approval of the therapeutic use of monoclonal antibodies against immune checkpoint molecules, notably those that target the proteins PD-1 and PD-L1, has changed the landscape of cancer treatment. In particular, first-line PD-1/PD-L1 inhibitor drugs are increasingly common for the treatment of metastatic cancer, significantly prolonging patient survival. Despite the benefits brought by immune checkpoint inhibitors (ICIs)-based therapy, the majority of patients had their diseases worsen following a promising initial response. To increase the effectiveness of ICIs and advance our understanding of the mechanisms causing cancer resistance, it is crucial to find new, effective, and tolerable combination treatments. In this article, we addressed the potential of ICIs for the treatment of solid tumors and offer some insight into the molecular pathways behind therapeutic resistance to ICIs. We also discuss cutting-edge therapeutic methods for reactivating T-cell responsiveness after resistance has been established.

Keywords: Acquired resistance; Breast cancer; Glioblastoma; Immune checkpoint inhibitor (ICIs); Immunotherapy; Melanoma; Non-small cell lung cancer; Prostate cancer; Renal cell carcinoma.

Publication types

Review