Killer immunoglobulin-like receptor genotype did not correlate with response to anti-PD-1 antibody treatment in a Japanese cohort

Yoshihiro Ishida,Yuki Yamamoto,Chisa Nakashima,Hidenori Tanaka,Yasuhiro Fujisawa,Shigeto Matsushita,Hiroto Kojima,Atsushi Otsuka,Taku Fujimura,Koji Yoshino,Kenji Kabashima

doi:10.1038/s41598-018-34044-z

Abstract

Immune checkpoint blockade (ICB) induces a remarkable response in patients with certain cancers. However, the response rate is not yet satisfactory. Biomarkers that help physicians identify patients who would benefit from ICB need to be developed. Killer immunoglobulin-like receptors (KIRs) are a class of receptors that are mainly expressed by natural killer cells. KIR genotypes have been shown to influence the outcomes of patients with neuroblastoma and hematopoietic malignancies. KIRs may thus influence the clinical outcomes of melanoma patients receiving nivolumab. We aimed to identify the KIR genotype, or KIR/KIR-ligand combinations, which influence the outcomes of melanoma patients receiving nivolumab. We genotyped 112 melanoma patients who were treated with nivolumab for KIR and human leukocyte antigen. The clinical records of the patients were analyzed to determine if they showed a response to nivolumab, and whether or not they experienced adverse events. Our analysis showed that no KIR gene was associated with a response to nivolumab. The KIR/KIR-ligand combination did not correlate with a response to nivolumab. KIR genes were not predictive of experiencing adverse events of grade 2 or greater. We conclude that the KIR genotype or KIR/KIR-ligand genotype do not show predictive value in melanoma patients receiving nivolumab.

Highlights

Immune checkpoint blockade (ICB) has revolutionized the management of malignancies, there remain a considerable number of patients who do not respond
In light of the pressing need to develop biomarkers for ICB, we asked if the Killer immunoglobulin-like receptors (KIRs) or compound KIR–ligand genotype predicts the outcome of ICB by studying melanoma patients treated with nivolumab
We asked if immune-related adverse events caused by ICB are associated with the KIR genotypes because they emulate autoimmune diseases, such as interstitial pneumonia, Hashimoto’s thyroiditis, and type 1 diabetes, some of which were shown to be influenced by KIR genotypes[11,12]

Summary

Introduction

Immune checkpoint blockade (ICB) has revolutionized the management of malignancies, there remain a considerable number of patients who do not respond. These biomarkers include serum lactate dehydrogenase level[1], baseline lymphocyte to neutrophil ratio[2], PD-L1 expression of tumor cells[3], mutational load[4], gut microbiome[5], and human leukocyte antigen (HLA) allele of the host[6,7]. In light of the pressing need to develop biomarkers for ICB, we asked if the KIR or compound KIR–ligand genotype predicts the outcome of ICB by studying melanoma patients treated with nivolumab. We report that the KIR or KIR–ligand genotype does not influence the clinical outcomes of melanoma patients receiving nivolumab therapy

Objectives

Results

Conclusion