PD-1/PD-L1 blockade in cancer treatment: perspectives and issues.

Junzo Hamanishi,Noriomi Matsumura,Tsukasa Baba,Kaoru Abiko,Masaki Mandai,Ikuo Konishi

doi:10.1007/s10147-016-0959-z

Junzo Hamanishi, Noriomi Matsumura + Show 4 more

Open Access

https://doi.org/10.1007/s10147-016-0959-z

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Abstract

Recent studies showed that tumor cells ‘edit’ host immunity in several ways to evade immune defenses in the tumor microenvironment. This phenomenon is called “cancer immune escape.” One of the most important components in this system is an immunosuppressive co-signal (immune checkpoint) mediated by the PD-1 receptor and its ligand, PD-L1. PD-1 is mainly expressed on activated T cells, whereas PD-L1 is expressed on several types of tumor cells. Preclinical studies have shown that inhibition of the interaction between PD-1 and PD-L1 enhances the T-cell response and mediates antitumor activity. Several clinical trials of PD-1/PD-L1 signal-blockade agents have exhibited dramatic antitumor efficacy in patients with certain types of solid or hematological malignancies. In this review, we highlight recent clinical trials using anti-PD-1 or anti-PD-L1 antibodies against several types of malignancies, including a trial conducted in our department, and describe the clinical perspectives and issues regarding the PD-1/PD-L1 blockade in cancer treatment.

Highlights

Tumor cells have acquired several ways to escape from host immunity in the tumor microenvironment, called cancer immune escape via cancer immunoediting process [1]
To judge the value of programmed cell death-1 (PD-1) pathway inhibitors, there is an urgent need to establish patient selection methods based on biomarkers, permitting prediction of the efficacy and adverse effects (AEs) of PD-1 pathway inhibitors
More than 20 years after the discovery of PD-1 [1], several studies have identified the clinical efficacy of PD-1 blockade against a wide spectrum of solid and hematological malignancies, opening the door to a strategy for the treatment of cancer

Summary

Introduction

Tumor cells have acquired several ways to escape from host immunity in the tumor microenvironment, called cancer immune escape via cancer immunoediting process [1]. The estimated 6-month progression-free survival rates were 47 %, 46.4 %, Representative phase II or III clinical trials with anti-PD-1 antibodies, nivolumab and pembrolizumab, in patients with non-small cell lung cancer (NSCLC) are described here. The results revealed durable clinical efficacy in 11 subjects, and the mutation levels in these patients were significantly elevated [81] Because neither of these factors is sufficient as a predictive marker for treatment, genomewide somatic cell neo-epitope analysis and HLA analysis were carried out, resulting in identification of a neo-epitope candidate that is expressed in tumors against which anti-CTLA-4 antibodies are therapeutically effective. To judge the value of PD-1 pathway inhibitors, there is an urgent need to establish patient selection methods based on biomarkers, permitting prediction of the efficacy and AEs of PD-1 pathway inhibitors

Conclusion

Findings

Compliance with ethical standards