Immune-related aseptic meningitis diagnosed by Cube FLAIR on enhanced magnetic resonance imaging for a lung cancer patient administered atezolizumab: A case report

Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs), such as neurological toxicity. A 46-year-old man was diagnosed with squamous cell lung cancer. Lung cancer recurred 3 years after he experienced left segmental lung rejection. Therefore, he received atezolizumab as fourth-line chemotherapy. He experienced fever, headache, and decreased consciousness 10 days after the first dose of atezolizumab. Plain head computed tomography and cerebrospinal fluid examination showed no significant findings. Magnetic resonance imaging (MRI) with a Gadolinium (Gd)-enhanced Cube fluid-attenuated inversion recovery (FLAIR) sequence showed nodular abnormalities with contrast enhancement. Thus, aseptic meningitis caused by ICIs was suspected. His consciousness level gradually improved with glucocorticoid therapy. Moreover, most nodular abnormalities observed on cerebral MRI disappeared concurrently. Thus, Gd-enhanced Cube FLAIR sequence has the unique ability to reveal immune-related aseptic meningiti

Hepatic stellate cells relay inflammation signaling from sinusoids to parenchyma in mouse models of immune-mediated hepatitis.

ビタミンAを貯蔵する肝星細胞が肝臓の炎症を制御していた --肝炎、肝硬変、肝癌の予防や治療法開発に期待--. 京都大学プレスリリース. 2015-10-15.Issue published online: 23 MAR 2016Hepatic stellate cells (HSCs) constitute the liver sinusoid with Kupffer cells and liver sinusoidal endothelial cells. While the sinusoid functions as the gateway to liver inflammation, whether HSCs contribute to liver inflammation and, if so, how they exert such functions remain elusive. Here, we found that mouse as well as human HSCs expressed DP1 receptor for prostaglandin D2 selectively in the liver. Pharmacological stimulation of DP1 by BW245C, a DP1-selective agonist, suppressed the activation of cultured HSCs by tumor necrosis factor-α at least in part through down-regulation of nuclear factor kappa-light-chain-enhancer of activated B cells signaling and inhibition of c-Jun N-terminal kinase phosphorylation. DP1 deficiency or BW245C administration in mice significantly enhanced or suppressed concanavalin A (ConA)-induced hepatitis, respectively. ConA injection induced tumor necrosis factor-α and interferon-γ expression in the sinusoid, which was suppressed by administration of BW245C. Coculture of spleen cells and liver nonparenchymal cells showed that ConA first activated spleen cells and that this activation led to activation of nonparenchymal cells to secondarily produce tumor necrosis factor-α and interferon-γ. Microarray analysis revealed ConA-induced expression of endothelin-1, tissue factor, and chemokines in the liver and inducible nitric oxide synthase in hepatocytes, resulting in flow stagnation, leukocyte adherence and migration to the parenchyma, and hepatocyte death. DP1 stimulation inhibits all these events in the liver. Therefore, HSCs mediate amplification of ConA-induced liver inflammation in the sinusoid, causing direct and indirect hepatocyte injury, and DP1 stimulation inhibits this HSC activation

Immune‐related aseptic meningitis diagnosed by Cube FLAIR on enhanced magnetic resonance imaging for a lung cancer patient administered atezolizumab: A case report

Abstract Immune checkpoint inhibitors (ICIs) can cause immune‐related adverse events (irAEs), such as neurological toxicity. A 46‐year‐old man was diagnosed with squamous cell lung cancer. Lung cancer recurred 3 years after he experienced left segmental lung rejection. Therefore, he received atezolizumab as fourth‐line chemotherapy. He experienced fever, headache, and decreased consciousness 10 days after the first dose of atezolizumab. Plain head computed tomography and cerebrospinal fluid examination showed no significant findings. Magnetic resonance imaging (MRI) with a Gadolinium (Gd)‐enhanced Cube fluid‐attenuated inversion recovery (FLAIR) sequence showed nodular abnormalities with contrast enhancement. Thus, aseptic meningitis caused by ICIs was suspected. His consciousness level gradually improved with glucocorticoid therapy. Moreover, most nodular abnormalities observed on cerebral MRI disappeared concurrently. Thus, Gd‐enhanced Cube FLAIR sequence has the unique ability to reveal immune‐related aseptic meningiti