Objective: To develop a neoantigen-targeted personalized cancer treatment for non-small cell lung cancer (NSCLC), neoantigens were obtained from collected human lung cancer samples, and the utility of neoantigen and neoantigen-reactive T cells (NRTs) was assessed.Methods: Tumor specimens from three patients with NSCLC were obtained and analyzed by whole-exome sequencing, and neoantigens were predicted accordingly. Dendritic cells and T lymphocytes were isolated, NRTs were elicited and IFN-γ ELISPOT tests were conducted. HLA-A2.1/K^b transgenic mice were immunized with peptides from HLA-A*02:01⁺patient with high immunogenicity, and NRTs were subjected to IFN-γ, IL-2 and TNF-α ELISPOT as well as time-resolved fluorescence assay for cytotoxicity assays to verify the immunogenicity in vitro. The HLA-A*02:01⁺lung cancer cell line was transfected with minigene and inoculated into the flanks of C57BL/6^nu/nu mice and the NRTs induced by the immunogenic polypeptides from autologous HLA-A2.1/K^b transgenic mice were adoptively transfused to verify their immunogenicity in vivo.Results: Multiple putative mutation-associated neoantigens with strong affinity for HLA were selected from each patient. Immunogenic neoantigen were identified in all three NSCLC patients, the potency of ACAD8-T105I, BCAR1-G23V and PLCG1-M425L as effective neoantigen to active T cells in suppressing tumor growth was further proven both in vitro and in vivo using HLA-A2.1/Kb transgenic mice and tumor-bearing mouse models.Conclusion: Neoantigens with strong immunogenicity can be screened from NSCLC patients through the whole-exome sequencing of patient specimens and machine-learning-based neoantigen predictions. NRTs shown efficient antitumor responses in transgenic mice and tumor-bearing mouse models. Our results indicate that the development of neoantigen-based personalized immunotherapies in NSCLC is possible.Precis: Neoantigens with strong immunogenicity were screened from NSCLC patients. This research provides evidence suggesting that neoantigen-based therapy might serve as feasible treatment for NSCLC.

Background: House dust mite (HDM) inhalation can cause airway epithelial damage which is implicated in the process of airway inflammation in asthma. High mobility group box 1 (HMGB1) is critically required for cellular damage and apoptosis as an important endogenous danger signal. Recently, Clara cell 16KDa protein (CC16) has been identified to exert anti-inflammatory and immunomodulatory influence in various injury-related diseases model. However, little is known about its ability to protect against airway epithelial injury in allergic asthma. This study was aimed to clarify the protective roles of CC16 on airway epithelia in HDM-induced asthma and the regulation of HMGB1 by CC16. Methods: Mice were sensitized and challenged by HDM extract and administrated intranasally with CC16 (5 μg/g or 10 μg/g) or saline in the challenged period. The BEAS-2B human airway epithelial cell line were cultured with CC16 or the control vehicle and then exposed to HDM. Knockdown or overexpression of HMGB1 was induced by cell transfection or intratracheal injection of recombinant adenovirus. Results: CC16 treatment decreased airway inflammation and histological damage of airway epithelium dose-dependently in HDM-induced asthma model. Airway epithelia apoptosis upon HDM stimulation was noticeably abrogated by CC16 in vivo and in vitro. In addition, upregulation of HMGB1 expression and its related signaling were also detected under HDM conditions, while silencing HMGB1 significantly inhibited the apoptosis of BEAS-2B cells. Furthermore, the activity of HMGB1-mediated signaling was restrained after CC16 treatment whereas HMGB1 overexpression abolished the protective effect of CC16 on HDM-induced airway epithelia apoptosis. Conclusions: Our data confirm that CC16 attenuates HDM-mediated airway inflammation and damage via suppressing airway epithelial cell apoptosis in a HMGB1-dependent manner, suggesting the role of CC16 as a potential protective option for HDM-induced asthma.

In most somatic tissues, adult stem cells are crucial for the maintenance of tissue homeostasis under normal physiological states and during recovery from injuries. Label retaining cell (LRC) assay remains the well-known method to identify possible somatic stem/progenitor cells and their location both in situ and in vivo. Here, BrdU was used to tag the possible hepatic stem/progenitor cells (HSPCs) in newborn pups, followed by a trace period of up to 23 months. Additionally, we report a method to rapidly kill proliferating cells in adult liver tissue, and activate and label (KAL) surviving possible HSPCs. We found that LRCs definitively exist in the liver tissues of adult mice, that LRCs express cell cycle proteins cyclind3 and cdk6, but do not express sca-1 or c-kit, and that LRCs locate primarily in the periportal and pericentral regions. Moreover, the number of these LRCs remains nearly constant during the lifespan of the mice. After injury induced by 5-fluorouracil, we observed that the activation of possible HSPCs tagged by the BrdU label was almost completely inhibited at day 4. The cellular kinetics of repair of BrdU-tagged HSPCs were different every 12 h between day 3 and day 4. Moreover, HSPCs still retained labels and located definitively in the periportal region after a prolonged chase. The LRC method together with our novel KAL method reported here may be used to identify and locate possible HSPCs.

Acute fibrinous and organizing pneumonia (AFOP) is a very rare form of acute or subacute lung injury, which is characterized by patches of “fibrin balls” distributed within the alveoli. Given the lack of typical clinical manifestations, AFOP is often misdiagnosed as pneumonia, tuberculosis, etc. Definitive diagnosis is obtained from a lung biopsy. Corticosteroids are usually effective. We report two cases of patients with histopathological manifestations of AFOP, which were significantly improved after corticosteroid therapy. Previous reports of the clinical and pathological characteristics of AFOP were reviewed to improve clinicians’ understanding of this disease. Early identification and diagnosis are very important for AFOP treatment. The prognosis is acceptable after timely and effective treatment.

The type II protein arginine methyltransferase 5 (PRMT5) has been engaged in various human cancer development and progression types. Nevertheless, few studies uncover the biological functions of PRMT5 in the epithelial-mesenchymal transition (EMT) of human lung cancer cells, and the associated molecular mechanisms and signaling cascades are entirely unknown. Here, we show that PRMT5 is the ectopic expression in human lung cancer tissues and cell lines. Further study reveals that silencing PRMT5 by lentivirus-mediated shRNA or blocking of PRMT5 by specific inhibitor GSK591 attenuates the expression levels of EMT-related markers in vivo, using the xenograft mouse model. Moreover, our results show that down-regulation of PRMT5 impairs EGFR/Akt signaling cascades in human lung cancer cells, whereas re-expression of PRMT5 recovers those changes, suggesting that PRMT5 regulates EMT probably through EGFR/Akt signaling axis. Altogether, our results demonstrate that PRMT5 serves as a critical oncogenic regulator and promotes EMT in human lung cancer cells. More importantly, our findings also suggest that PRMT5 may be a potential therapeutic candidate for the treatment of human lung cancer.

Background: Malignant melanoma (MM) generally presents as a primary neoplasm of the skin, and most MM cases of the respiratory system are metastatic. Primary MM of the lung (PMML) is quite rare, and its diagnosis is relatively difficult.Case presentation: We report the case of a 57-year-old male patient with PMML who denied any history of tumours. His initial complaint was frequent coughs with bloody sputum for 4 days. Chest radiography demonstrated a high-density shadow in the lower lobe of the right lung, which was suspected to be a large space-occupying lesion on subsequent computed tomography (CT) and to be a hypermetabolic tumour by positron emission tomography–CT. To confirm the diagnosis, exploratory surgery was performed. Finally, we confirmed the diagnosis of PMML.Conclusions: PMML is extremely rare and easily misdiagnosed as lung cancer. Because of its morphological and immunophenotypic variations, the diagnosis of PMML remains difficult. This case report discusses the diagnosis and case management of a patient while referring to the existing literature.