Osteopontin levels are elevated in patients with eosinophilic pneumonia

Background and objective: Osteopontin is a key cytokine involved in pro‐inflammatory T helper type 1 (Th1)‐associated immune responses, which has recently been implicated in allergic diseases. We investigated the pathogenic role of osteopontin in eosinophilic pneumonia. Methods: The concentrations of osteopontin and Th1‐ or Th2‐associated cytokines were measured in BAL fluid (BALF) from 41 patients with eosinophilic pneumonia, including those with acute (AEP, n = 12), chronic (CEP, n = 16), or drug‐induced eosinophilic pneumonia (DEP, n = 13). The results were compared with those from patients with other interstitial lung diseases. Immunocytochemistry and double immunofluorescence labelling were performed to determine the cellular source of osteopontin. Results: Osteopontin was significantly elevated in BALF from patients with eosinophilic pneumonia as compared with BALF from patients with drug‐induced interstitial pneumonia, hypersensitivity pneumonitis, idiopathic interstitial pneumonia, or sarcoidosis, and also compared with BALF from healthy volunteers. Osteopontin concentrations elevated at the time of exacerbation decreased during clinical improvement, either spontaneously or as a result of corticosteroid therapy. Elevated concentrations of CXCL10, CCL17 and IL‐10 were also detected in BALF from patients with eosinophilic pneumonia. Osteopontin concentrations in BALF of AEP patients were correlated with IL‐5, as well as IL‐10, CCL11, CCL17 and CXCL10 concentrations. In AEP and DEP patients, serum osteopontin concentrations were also elevated. Double immunofluorescence labelling showed that in patients with eosinophilic pneumonia, osteopontin was expressed in lung eosinophils. Conclusions: Osteopontin is likely to contribute to the development of inflammation in patients with eosinophilic pneumonia.     

A new clinicopathological entity of IgG4-related autoimmune disease

Background Autoimmune pancreatitis (AIP) is occasionally associated with other autoimmune diseases.Methods To investigate the pathophysiology of AIP, we immunohistochemically examined the pancreas and other organs in eight patients with AIP, and in controls, using anti-CD4-T and CD8-T cell subsets, as well as IgG4 antibodies.Results In AIP patients, severe or moderate infiltration of IgG4-positive plasma cells associated with CD4- or CD8-positive T lymphocytes was detected in the peripancreatic tissue (6/6), bile duct (8/8), gallbladder (8/8), portal area of the liver (3/3), gastric mucosa (5/7), colonic mucosa (2/2), salivary glands (1/2), lymph nodes (6/6), and bone marrow (2/2), as well as in the pancreas (8/8). There were few IgG4-positive plasma cells at the same sites in controls.Conclusions These results suggest that AIP is not simply pancreatitis but that it is a pancreatic lesion involved in IgG4-related systemic disease with extensive organ involvement. We propose a new clinicopathological entity, of a systemic IgG4-related autoimmune disease in which AIP and its associated diseases might be involved.     

Japanese Society of Medical Oncology/Japan Society of Clinical Oncology/Japanese Society of Pediatric Hematology/Oncology-led clinical recommendations on the diagnosis and use of immunotherapy in patients with high tumor mutational burden tumors

The development of novel antitumor agents and accompanying biomarkers has improved survival across several tumor types. Previously, we developed recommendations for tumor-agnostic treatments in patients with solid tumors with DNA mismatch repair deficient or neurotrophic receptor tyrosine kinase fusions. Recently, immune checkpoint inhibitors have shown efficacy in patient with tumor mutation burden-high (TMB-H) solid tumors and have been established as a third tumor-agnostic agent, making it necessary to develop the guideline prioritized for these patients. Clinical questions regarding medical care were formulated for patients with TMB-H advanced solid tumors. Relevant publications were searched by PubMed and Cochrane Database. Critical publications and conference reports were added manually. Systematic reviews were performed for each clinical question for the purpose of developing clinical recommendations. The committee members identified by Japan Society of Clinical Oncology (JSCO), Japanese Society of Medical Oncology (JSMO), and Japanese society of pediatric hematology/oncology (JSPHO) voted to determine the level of each recommendation considering the strength of evidence, expected risks and benefits to patients, and other related factors. Thereafter, a peer review by experts nominated from JSCO, JSMO, and JSPHO, and the public comments among all societies' members was done. The current guideline describes three clinical questions and seven recommendations for whom, when, and how TMB should be tested, and what is recommended for patients with TMB-H advanced solid tumors. In this guideline, the committee proposed seven recommendations for performing TMB testing properly to select patients who are likely to benefit from immunotherapy.

     

Japanese Society of Medical Oncology/Japan Society of Clinical Oncology/Japanese Society of Pediatric Hematology/Oncology-led clinical recommendations on the diagnosis and use of tropomyosin receptor kinase inhibitors in adult and pediatric patients with neurotrophic receptor tyrosine kinase fusion-positive advanced solid tumors

Background

Clinical trials have reported the efficacy of tropomyosin receptor kinase (TRK) inhibitors against neurotrophic receptor tyrosine kinase (NTRK) fusion gene-positive advanced solid tumors. The accumulated evidence of tumor-agnostic agent has made since TRK inhibitors were approved and used in clinical practice. Therefore, we have revised the ‘Japan Society of Clinical Oncology (JSCO)/Japanese Society of Medical Oncology (JSMO)-led clinical recommendations on the diagnosis and use of tropomyosin receptor kinase inhibitors in adult and pediatric patients with neurotrophic receptor tyrosine kinase fusion-positive advanced solid tumors, cooperated by the Japanese Society of Pediatric Hematology/Oncology (JSPHO)’.

Methods

Clinical questions regarding medical care were formulated for patients with NTRK fusion-positive advanced solid tumors. Relevant publications were searched by PubMed and Cochrane Database. Critical publications and conference reports were added manually. Systematic reviews were performed for each clinical question for the purpose of developing clinical recommendations. The committee members identified by JSCO, JSMO, and JSPHO voted to determine the level of each recommendation considering the strength of evidence, expected risks and benefits to patients, and other related factors. Thereafter, a peer review by experts nominated from JSCO, JSMO, and JSPHO, and the public comments among all societies' members was done.

Results

The current guideline describes 3 clinical questions and 14 recommendations for whom, when, and how NTRK fusion should be tested, and what is recommended for patients with NTRK fusion-positive advanced solid tumors.

Conclusion

The committee proposed 14 recommendations for performing NTRK testing properly to select patients who are likely to benefit from TRK inhibitors.