Stephen Ahn

Purpose: The immune responses of natural killer (NK) cells against cancer cells vary by patient. Killer Ig-like receptors (KIRs), which are some of the major receptors involved in regulating NK cell activity for killing cancer cells, have significant genetic variation. Numerous studies have suggested a potential association between the genetic variation of KIR genes and the risk of development or prognosis of various cancer types. However, an association between genetic variations of KIR genes and glioblastoma (GB) remains uncertain. We sought to evaluate the association of genetic variations of KIRs and their ligand genes with the risk of GB development in Koreans. Methods: A case–control study was performed to identify the odds ratios (ORs) of KIR genes and Classes A, B, and, C of the human leukocyte antigen (HLA) for GB. The GB group was comprised of 77 patients with newly diagnosed IDH-wildtype GB at our institution, and the control group consisted of 200 healthy Korean volunteers. Results: There was no significant difference in the frequency of KIR genes and KIR haplotypes between the GB and control groups. Genetic variations of KIR-2DL1, 3DL1, and 3DS1 with their ligand genes (HLA-C2, HLA-Bw4/6, and Bw4, respectively) had effects on the risk of GB in Korean patients. The frequency of KIR-2DL1 with HLA-C2 (OR 2.05, CI 1.19–3.52, p = 0.009), the frequency of KIR-3DL1 without HLA-Bw4 (80I) (OR 8.36, CI 4.06–17.18, p < 0.001), and the frequency of KIR-3DL1 with Bw6 (OR 4.54, CI 2.55–8.09, p < 0.001) in the GB group were higher than in the control group. In addition, the frequency of KIR-2DL1 without HLA-C2 (OR 0.44, CI 0.26–0.75, p = 0.003), the frequency of KIR-3DL1 with HLA-Bw4 (80T) (OR 0.13, CI 0.06–0.27, p < 0.001), the frequency of KIR-3DL1 without Bw6 (OR 0.27, CI 0.15–0.49, p < 0.001), and the frequency of KIR-3DS1 with Bw4 (80I) (OR 0.03, CI 0.00–0.50, p < 0.001) in the GB group were lower than in the control group. Conclusions: This study suggests that genetic variations of KIRs and their ligand genes may affect GB development in the Korean population. Further investigations are needed to demonstrate the different immune responses for GB cells according to genetic variations of KIR genes and their ligand genes.

Purpose Addressing lymphopenia in cancer patients has been suggested as a novel immunotherapeutic strategy. As interleukin‐7 (IL‐7) is necessary for proliferation of lymphocytes and to increase total lymphocyte count (TLC), IL‐7 therapy has been attempted in various cancers. Here, we describe the clinical results of treatment of recurrent glioblastoma (GBM) with a long‐acting engineered version of recombinant human IL‐7 (rhIL‐7‐hyFc). Methods This prospective case series based on compassionate use was approved by the Ministry of Food and Drug Safety in South Korea. Primary outcomes were safety profile and TLC. Secondary outcomes were overall survival (OS) and progression‐free survival (PFS). Results Among the 18 patients enrolled, 10 received rhIL‐7‐hyFc with temozolomide, 5 received rhIL‐7‐hyFc with bevacizumab, 1 received rhIL‐7‐hyFc with PCV chemotherapy, and 2 received rhIL‐7‐hyFc alone. Mean TLC of the enrolled patients after the first rhIL‐7‐hyFc treatment increased significantly from 1131 cells/mm 3 (330–2989) at baseline to 4356 cells/mm 3 (661–22,661). Higher TLCs were maintained while rhIL‐7‐hyFc was repeatedly administered. Median OS and PFS were 378 days (107–864 days) and 231 days (55–726 days), respectively. Conclusion Our study reports that IL‐7 immunotherapy can restore and maintain TLC during treatment with various salvage chemotherapies in recurrent GBM patients without serious toxicity.