SARS-CoV-2 is a spherical, enveloped, single-stranded positive RNA virus with a diameter of 80 nm-160 nm and a genome size of 29.9 kb

ObjectiveProgrammed death 1 and its ligand 1 (PD-1/PD-L1) immunotherapy is promising for late-stage lung cancer treatment, however, the response rate needs to be improved. Gut microbiota plays a crucial role in immunotherapy sensitisation and Panax ginseng has been shown to possess immunomodulatory potential. In this study, we aimed to investigate whether the combination treatment of ginseng polysaccharides (GPs) and αPD-1 monoclonal antibody (mAb) could sensitise the response by modulating gut microbiota.DesignSyngeneic mouse models were administered GPs and αPD-1 mAb, the sensitising antitumour effects of the combination therapy on gut microbiota were assessed by faecal microbiota transplantation (FMT) and 16S PacBio single-molecule real-time (SMRT) sequencing. To assess the immune-related metabolites, metabolomics analysis of the plasma samples was performed.ResultsWe found GPs increased the antitumour response to αPD-1 mAb by increasing the microbial metabolites valeric acid and decreasing L-kynurenine, as well as the ratio of Kyn/Trp, which contributed to the suppression of regulatory T cells and induction of Teff cells after combination treatment. Besides, the microbial analysis indicated that the abundance of Parabacteroides distasonis and Bacteroides vulgatus was higher in responders to anti-PD-1 blockade than non-responders in the clinic. Furthermore, the combination therapy sensitised the response to PD-1 inhibitor in the mice receiving microbes by FMT from six non-responders by reshaping the gut microbiota from non-responders towards that of responders.ConclusionOur results demonstrate that GPs combined with αPD-1 mAb may be a new strategy to sensitise non-small cell lung cancer patients to anti-PD-1 immunotherapy. The gut microbiota can be used as a novel biomarker to predict the response to anti-PD-1 immunotherapy.

The tumor microenvironment (TME) is a complex ecosystem, which includes many different types of cells, abnormal vascular systems, and immunosuppressive cytokines. TME serves an important function in tumor tolerance and escapes from immune surveillance leading to tumor progression. Indeed, there is increasing evidence that gut microbiome is associated with cancer in a variety of ways, as specific microbial signatures are known to promote cancer development and influence safety, tolerability, and efficacy of therapies. Studies over the past five years have shown that the composition of the intestinal microbiota has a significant impact on the efficacy of anticancer immunosurveillance, which contribute to the therapeutic activity of cancer immunotherapies based on targeting cytotoxic T lymphocyte protein 4 (CTLA-4) or programmed cell death protein 1 (PD-1)–programmed cell death 1 ligand 1 (PD-L1) axis. In this review, we mainly discuss the impact of TME on cancer and immunotherapy through immune-related mechanisms. We subsequently discuss the influence of gut microbiota and its metabolites on the host immune system and the formation of TME. In addition, this review also summarizes the latest research on the role of gut microbiota in cancer immunotherapy.

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As an iron-dependent mode of programmed cell death induced by lipid peroxidation, ferroptosis plays an important role in cancer therapy. The metabolic reprogramming in tumor microenvironment allows the possibility of targeting ferroptosis in cancer treatment. Recent studies reveal that nanomaterials targeting ferroptosis have prospects for the development of new cancer treatments. However, the design ideas of nanomaterials targeting ferroptosis sometimes vary. Therefore, in addition to the need for a systematic summary of these ideas, new ideas and insights are needed to make possible the construction of nanomaterials for effectively targeting this cell death pathway. At the same time, further optimization of nanomaterials design is required to make them appropriate for clinical treatment. In this context, we summarize this cross-cutting research area covering from the known mechanism of ferroptosis to providing feasible ideas for nanomaterials design as well as their clinical application. We aim to provide new insights and enlightenment for the next step in developing new nanomaterials for cancer treatment.

Aberrant signaling transduction induced by mutant KRAS proteins occurs in 20∼30% of non-small cell lung cancer (NSCLC), however, a direct and effective pharmacological inhibitor targeting KRAS has not yet reached the clinic to date. Honokiol, a small molecular polyphenol natural biophenolic compound derived from the bark of magnolia trees, exerts anticancer activity, however, its mechanism remains unknown. In this study, we sought to investigate the in vitro effects of honokiol on NSCLC cell lines harboring KRAS mutations. Honokiol was shown to induce G1 arrest and apoptosis to inhibit the growth of KRAS mutant lung cancer cells, which was weakened by an autophagy inhibitor 3-methyladenine (3-MA), suggesting a pro-apoptotic role of honokiol-induced autophagy that was dependent on AMPK-mTOR signaling pathway. In addition, we also discovered that Sirt3 was significantly up-regulated in honokiol treated KRAS mutant lung cancer cells, leading to destabilization of its target gene Hif-1α, which indicated that the anticancer property of honokiol maybe regulated via a novel mechanism associated with the Sirt3/Hif-1α. Taken together, these results broaden our understanding of the mechanisms on honokiol effects in lung cancer, and reinforce the possibility of its potential anticancer benefit as a popular Chinese herbal medicine (CHM).

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The Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 has been rapidly spreading globally and has caused worldwide social and economic disruption. Currently, no specific antiviral drugs or clinically effective vaccines are available to prevent and treat COVID-19. Traditional Chinese medicine (TCM) can facilitate syndrome differentiation and treatment according to the clinical manifestations of patients and has demonstrated effectiveness in epidemic prevention and control. In China, TCM intervention has helped to control the epidemic; however, TCM has not been fully recognized worldwide. In this review, we summarize the epidemiology and etiological characteristics of severe acute respiratory syndrome coronavirus 2 and the prevention and treatment measures of COVID-19. Additionally, we describe the application of TCM in the treatment of COVID-19 and the identification of small molecules of TCM that demonstrate anti-coronavirus activity. We also analyze the current problems associated with the recognition of TCM. We hope that, through the contribution of TCM, combined with modern technological research and the support of our international counterparts, COVID-19 can be effectively controlled and treated.