Translational research : the journal of laboratory and clinical medicine
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The advent of liquid biopsies has brought significant changes to the diagnosis and monitoring of non-small cell lung cancer (NSCLC), presenting both promise and challenges. Molecularly targeted drugs, capable of enhancing survival rates, are now available to around a quarter of NSCLC patients. However, to ensure their effectiveness, precision diagnosis is essential. ⋯ Liquid biopsy analysis bears the potential of transforming NSCLC management by enabling non-invasive monitoring of Minimal Residual Disease and providing early indicators for response to targeted treatments including immunotherapy. Furthermore, considerations regarding sample collection, processing, and data interpretation are highlighted as crucial factors influencing the reliability and reproducibility of ctDNA-based assays. Addressing these challenges will be essential for the widespread adoption of ctDNA-based liquid biopsies in routine clinical practice, ultimately paving the way toward personalized medicine and improved outcomes for patients with NSCLC.
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Mammalian lung is the important organ for ventilation and exchange of air and blood. Fresh air and venous blood are constantly delivered through the airway and vascular tree to the alveolus. Based on this, the airways and alveolis are persistently exposed to the external environment and are easily suffered from toxins, irritants and pathogens. ⋯ Meanwhile, we emphasize that interaction between the lung epithelial cells and innate immune cells is more supportive to repair and regenerate in the lung epithelium following acute lung injury. We reviewed the recent advances in injury and repair of lung epithelial stem cells and innate immune cells in ALI/ARDS, concentrating on alveolar type 2 cells and alveolar macrophages and their contribution to post-injury repair behavior of ALI/ARDS through the latest potential molecular communication mechanisms. This will help to develop new research strategies and therapeutic targets for ALI/ARDS.
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Lung cancer has been shown to be targetable by novel immunotherapies which reactivate the immune system and enable tumor cell killing. However, treatment failure and resistance to these therapies is common. Consideration of sex as a factor influencing therapy resistance is still rare. ⋯ Moreover, glycodelin colocalizes to tumor infiltrating CD8+ T cells and pro-tumorigenic M2 macrophages. High serum concentrations of glycodelin prior to immunotherapy are associated with a poor progression-free survival (p < 0.001) of female patients receiving PD-(L)1 inhibitors. In summary, our findings suggest that glycodelin not only is a promising immunological biomarker for early identification of female patients that do not benefit from the costly immunotherapy, but also represents a promising immunotherapeutic target in NSCLC to improve therapeutic options in lung cancer.
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Glioblastoma (GBM) is the most frequent and aggressive primary brain cancer. The Src inhibitor, TAT-Cx43266-283, exerts antitumor effects in in vitro and in vivo models of GBM. Because addressing the mechanism of action is essential to translate these results to a clinical setting, in this study we carried out an unbiased proteomic approach. ⋯ Our results were consistent with the inhibition of Src as the mechanism of action of TAT-Cx43266-283 and unveiled antitumor effectors, such as p120 catenin. Changes in the abundance of several proteins suggested that TAT-Cx43266-283 may also impact the brain microenvironment. Importantly, the proteins whose abundance was reduced by TAT-Cx43266-283 correlated with an improved GBM patient survival in clinical datasets and none of the proteins whose abundance was increased by TAT-Cx43266-283 correlated with shorter survival, supporting its use in clinical trials.
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The Proprotein Convertase Subtilisin Kexin of type 9 (PCSK9) has been identified in 2003 as the third gene involved in familial hypercholesterolemia. PCSK9 binds to the membrane low-density lipoprotein receptor (LDLR) and promotes its cellular internalization and lysosomal degradation. Beyond this canonical role, PCSK9 was recently described to be involved in several immune responses. ⋯ Interestingly, the protective effect of PCSK9 inhibition against food allergy symptoms was independent of the LDLR as PCSK9 inhibitors remained effective in Ldlr deficient mice. In vitro, we showed that recombinant gain of function PCSK9 (PCSK9 D374Y) increased the percentage of mature bone marrow derived dendritic cells (BMDCs), promoted naïve T cell proliferation and potentiated the gliadin induced basophils degranulation. Altogether, our data demonstrate that PCSK9 inhibition is protective against gliadin induced food allergy in a LDLR-independent manner.