Clinical Applications of Natural Killer Cells

Natural killer (NK) cells are an essential component of the innate immune system, and they play a crucial role in immunity against malignancies. Recent advances in our understanding of NK cell biology have paved the way for new therapeutic strategies based on NK cells for the treatment of various cancers. In this section, we will focus on NK cell immunotherapy, including the enhancement of antibody‐dependent cellular cytotoxicity, the manipulation of receptor‐mediated activation, inclusion criteria based on killer cell immunoglobulin‐like receptor (KIR) ligand mismatches, and adoptive immunotherapy with ex vivo expanded chimeric antigen receptor (CAR)‐engineered or engager‐modified NK cells. In contrast to T lymphocytes, donor NK cells do not attack any recipient tissues based on allogeneic human leukocyte antigens (HLAs), suggesting that NK‐mediated antitumor effects may be achieved without the risk of graft‐versus‐host disease (GvHD). Despite reports of clinical efficacy, the application of NK cell immunotherapy is limited. Developing strategies for manipulating NK cell products, host factors, and tumor targets are thus current subjects of diligent study. Research into the biology of NK cells has indicated that NK cell immunotherapy has the potential to become the forefront of cancer immunotherapy in the coming years

Subtle changes in strain prior to sub-Plinian eruptions recorded by vault-housed extensometers during the 2011 activity at Shinmoe-dake, Kirishima volcano, Japan

This study focuses on strain change observations with a precision of 10-9 associated with the 2011 Shinmoe-dake eruptions in Japan, using vault-housed extensometers installed approximately 18 km northwest of the Shinmoe-dake crater. The extensometers recorded major strain changes of 10-7 during three sub-Plinian eruptions and subsequent magma effusion. Our analysis indicates that these extensometer records provide a reasonable estimation of the parameters of an isotropic point source that can explain eruption-related ground deformation. The extensometers also recorded subtle strain changes of 10-9 prior to the three sub-Plinian eruptions. Time series data indicate that changes in strain at these rates are generally only observed immediately before explosive eruptions, suggesting that these strain changes are precursors to sub-Plinian eruptions. The source of these subtle strain changes is likely to be shallower than the magma chamber associated with these eruptions. The precursory strain changes might have been caused by a pressure increase and a subsequent pressure decrease under the volcano. One possible scenario that can explain these pressure changes is the accumulation of volcanic gases at depth, causing an increase in pressure that was eventually released during gas emissions from the crater prior to the explosive eruptions

Clinical implications of the novel cytokine IL-38 expressed in lung adenocarcinoma: Possible association with PD-L1 expression.

Interleukin (IL)-38, a novel member of the IL-1 cytokine family, is homologous to IL-1 receptor antagonist (IL-1Ra) and IL-36Ra, and has been reported to act as an antagonist. IL-38 expression is found in tonsil, placenta, and spleen, and recent studies suggest an association between IL-38 and autoimmune diseases. However, whether IL-38 plays a role in carcinogenesis or cancer growth is unclear. In the present study, we identified increases in IL-38 expression by immunohistochemistry in multiple types of cancer cells. In the examination of 417 surgically resected primary lung adenocarcinomas, Fisher's exact tests showed significant associations between high IL-38 expression and high tumor grades, an advanced T status, advanced N status, advanced stage, and the presence of pleural and vessel invasions. Survival analyses by the Kaplan-Meier method showed that patients with high expression of IL-38 had significantly shorter disease-free survival and shorter overall survival after surgery than patients with low expression of IL-38 (log-rank test: P = 0.0021 and P = 0.0035, respectively). Moreover, programmed cell death-ligand 1 (PD-L1)-positive cases showed higher expression of IL-38 than PD-L1-negative cases (Wilcoxon rank-sum test: P < 0.0001). In conclusion, IL-38 was expressed in tumor cells of various cancers, and IL-38 expression was associated with poor survival of lung adenocarcinoma patients. IL-38 may affect host immunity or the tumor microenvironment, and contribute to the progression of lung adenocarcinoma

Univariate and multivariate analyses of the relationship between IL-38 expression and other patient characteristics.

<p>Univariate and multivariate analyses of the relationship between IL-38 expression and other patient characteristics.</p

Univariate and multivariate analyses of DFS and OS in patients with primary lung adenocarcinoma.

<p>Univariate and multivariate analyses of DFS and OS in patients with primary lung adenocarcinoma.</p

Clinicopathological characteristics of patients with primary lung adenocarcinoma.

<p>Clinicopathological characteristics of patients with primary lung adenocarcinoma.</p

Representative images of (left panel) HE staining, (middle panel) IL-38 staining, and (right panel) negative controls.

<p>(A) Human tonsil tissue. (B) Human placenta tissue. (C) Human spleen tissue. HE: Hematoxylin-eosin, IL-38: interleukin-38. Scale bar: 100 μm.</p

Kaplan-Meier curves according to IL-38 expression in the analysis of PD-L1-negative cases and PD-L1-positive cases.

<p>Kaplan-Meier curves showing (A, C) disease-free and (B, D) overall survival of primary lung adenocarcinoma patients according to IL-38 expression in the analysis of (A, B) PD-L1-negative cases and (C, D) PD-L1-positive cases. IL-38: interleukin-38, PD-L1: programmed cell death-ligand 1.</p

Association between IL-38 expression and clinicopathological factors in patients with primary lung adenocarcinoma.

<p>Association between IL-38 expression and clinicopathological factors in patients with primary lung adenocarcinoma.</p

Association between PD-L1 and IL-38 expression.

<p>(A) PD-L1-positive cases showed higher expression of IL-38 than PD-L1-negative cases (Wilcoxon rank-sum test: <i>P</i> < 0.0001). (B) Representative images of (upper panel) PD-L1 staining and (lower panel) IL-38 staining in a (left panel) PD-L1-negative case and (right panel) PD-L1-positive case. IHC: immunohistochemistry, PD-L1: programmed cell death-ligand 1, IL-38: interleukin-38. Scale bar: 100 μm.</p