Guangdong Medical College

autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

BACKGROUND: The outbreak of 2019 novel coronavirus disease (COVID-19) in Wuhan, China, has spread rapidly worldwide. In the early stage, we encountered a small but meaningful number of patients who were unintentionally scheduled for elective surgeries during the incubation period of COVID-19. We intended to describe their clinical characteristics and outcomes. METHODS: We retrospectively analyzed the clinical data of 34 patients underwent elective surgeries during the incubation period of COVID-19 at Renmin Hospital, Zhongnan Hospital, Tongji Hospital and Central Hospital in Wuhan, from January 1 to February 5, 2020. FINDINGS: Of the 34 operative patients, the median age was 55 years (IQR, 43-63), and 20 (58·8%) patients were women. All patients developed COVID-19 pneumonia shortly after surgery with abnormal findings on chest computed tomographic scans. Common symptoms included fever (31 [91·2%]), fatigue (25 [73·5%]) and dry cough (18 [52·9%]). 15 (44·1%) patients required admission to intensive care unit (ICU) during disease progression, and 7 patients (20·5%) died after admission to ICU. Compared with non-ICU patients, ICU patients were older, were more likely to have underlying comorbidities, underwent more difficult surgeries, as well as more severe laboratory abnormalities (eg, hyperleukocytemia, lymphopenia). The most common complications in non-survivors included ARDS, shock, arrhythmia and acute cardiac injury. INTERPRETATION: In this retrospective cohort study of 34 operative patients with confirmed COVID-19, 15 (44·1%) patients needed ICU care, and the mortality rate was 20·5%. FUNDING: National Natural Science Foundation of China.

OBJECTIVES: To evaluate associations between different definitions of prediabetes and the risk of cardiovascular disease and all cause mortality. DESIGN: Meta-analysis of prospective cohort studies. DATA SOURCES: Electronic databases (PubMed, Embase, and Google Scholar). SELECTION CRITERIA: Prospective cohort studies from general populations were included for meta-analysis if they reported adjusted relative risks with 95% confidence intervals for associations between the risk of composite cardiovascular disease, coronary heart disease, stroke, all cause mortality, and prediabetes. REVIEW METHODS: ) of 39-47 mmol/mol : (5.7-6.4%) according to ADA criteria or 42-47 mmol/mol (6.0-6.4%) according to the National Institute for Health and Care Excellence (NICE) guideline. The relative risks of all cause mortality and cardiovascular events were calculated and reported with 95% confidence intervals. RESULTS: to 39-47 mmol/mol or 42-47 mmol/mol were both associated with an increased risk of composite cardiovascular disease (1.21 and 1.25, respectively) and coronary heart disease (1.15 and 1.28, respectively), but not with an increased risk of stroke and all cause mortality. CONCLUSIONS: of 39 mmol/mol.

Objective N 6 -methyladenosine (m 6 A) RNA methylation and its associated methyltransferase METTL3 are involved in tumour initiation and progression via the regulation of RNA function. This study explored the biological function and clinical significance of METTL3 in gastric cancer (GC). Design The prognostic value of METTL3 expression was evaluated using tissue microarray and immunohistochemical staining analyses in a human GC cohort. The biological role and mechanism of METTL3 in GC tumour growth and liver metastasis were determined in vitro and in vivo. Results The level of m 6 A RNA was significantly increased in GC, and METTL3 was the main regulator involved in the abundant m 6 A RNA modification. METTL3 expression was significantly elevated in GC tissues and associated with poor prognosis. Multivariate Cox regression analysis revealed that METTL3 expression was an independent prognostic factor and effective predictor in human patients with GC. Moreover, METTL3 overexpression promoted GC proliferation and liver metastasis in vitro and in vivo. Mechanistically, P300-mediated H3K27 acetylation activation in the promoter of METTL3 induced METTL3 transcription, which stimulated m 6 A modification of HDGF mRNA, and the m 6 A reader IGF2BP3 then directly recognised and bound to the m 6 A site on HDGF mRNA and enhanced HDGF mRNA stability. Secreted HDGF promoted tumour angiogenesis, while nuclear HDGF activated GLUT4 and ENO2 expression, followed by an increase in glycolysis in GC cells, which was correlated with subsequent tumour growth and liver metastasis. Conclusions Elevated METTL3 expression promotes tumour angiogenesis and glycolysis in GC, indicating that METTL3 expression is a potential prognostic biomarker and therapeutic target for human GC.

Mammalian target of rapamycin (mTOR) regulates cell proliferation, autophagy, and apoptosis by participating in multiple signaling pathways in the body. Studies have shown that the mTOR signaling pathway is also associated with cancer, arthritis, insulin resistance, osteoporosis, and other diseases. The mTOR signaling pathway, which is often activated in tumors, not only regulates gene transcription and protein synthesis to regulate cell proliferation and immune cell differentiation but also plays an important role in tumor metabolism. Therefore, the mTOR signaling pathway is a hot target in anti-tumor therapy research. In recent years, a variety of newly discovered mTOR inhibitors have entered clinical studies, and a variety of drugs have been proven to have high activity in combination with mTOR inhibitors. The purpose of this review is to introduce the role of mTOR signaling pathway on apoptosis, autophagy, growth, and metabolism of tumor cells, and to introduce the research progress of mTOR inhibitors in the tumor field.

The ubiquitin-proteasome system (UPS) and autophagy are two distinct and interacting proteolytic systems. They play critical roles in cell survival under normal conditions and during stress. An increasing body of evidence indicates that ubiquitinated cargoes are important markers of degradation. p62, a classical receptor of autophagy, is a multifunctional protein located throughout the cell and involved in many signal transduction pathways, including the Keap1-Nrf2 pathway. It is involved in the proteasomal degradation of ubiquitinated proteins. When the cellular p62 level is manipulated, the quantity and location pattern of ubiquitinated proteins change with a considerable impact on cell survival. Altered p62 levels can even lead to some diseases. The proteotoxic stress imposed by proteasome inhibition can activate autophagy through p62 phosphorylation. A deficiency in autophagy may compromise the ubiquitin-proteasome system, since overabundant p62 delays delivery of the proteasomal substrate to the proteasome despite proteasomal catalytic activity being unchanged. In addition, p62 and the proteasome can modulate the activity of HDAC6 deacetylase, thus influencing the autophagic degradation.

An active cell membrane-camouflaged nanoparticle, owning to membrane antigens and membrane structure, can achieve special properties such as specific recognition, long blood circulation, and immune escaping. Herein, we reported a cancer cell membrane-cloaked nanoparticle system as a theranostic nanoplatform. The biomimetic nanoparticles (indocyanine green (ICG)-loaded and cancer cell membrane-coated nanoparticles, ICNPs) exhibit a core-shell nanostructure consisting of an ICG-polymeric core and cancer cell membrane shell. ICNPs demonstrated specific homologous targeting to cancer cells with good monodispersity, preferable photothermal response, and excellent fluorescence/photoacoustic (FL/PA) imaging properties. Benefited from the functionalization of the homologous binding adhesion molecules from cancer cell membranes, ICNPs significantly promoted cell endocytosis and homologous-targeting tumor accumulation in vivo. Moreover, ICNPs were also good at disguising as cells to decrease interception by the liver and kidney. Through near-infrared (NIR)-FL/PA dual-modal imaging, ICNPs could realize real-time monitored in vivo dynamic distribution with high spatial resolution and deep penetration. Under NIR laser irradiation, ICNPs exhibited highly efficient photothermal therapy to eradicate xenografted tumor. The robust ICNPs with homologous properties of cancer cell membranes can serve as a bionic nanoplatform for cancer-targeted imaging and phototherapy.

The gut microbiota comprises a complex community of microorganism species that resides in our gastrointestinal ecosystem and whose alterations influence not only various gut disorders but also central nervous system disorders such as Alzheimer's disease (AD). AD, the most common form of dementia, is a neurodegenerative disorder associated with impaired cognition and cerebral accumulation of amyloid-β peptides (Aβ). Most notably, the microbiota-gut-brain axis is a bidirectional communication system that is not fully understood, but includes neural, immune, endocrine, and metabolic pathways. Studies in germ-free animals and in animals exposed to pathogenic microbial infections, antibiotics, probiotics, or fecal microbiota transplantation suggest a role for the gut microbiota in host cognition or AD-related pathogenesis. The increased permeability of the gut and blood-brain barrier induced by microbiota dysbiosis may mediate or affect AD pathogenesis and other neurodegenerative disorders, especially those associated with aging. In addition, bacteria populating the gut microbiota can secrete large amounts of amyloids and lipopolysaccharides, which might contribute to the modulation of signaling pathways and the production of proinflammatory cytokines associated with the pathogenesis of AD. Moreover, imbalances in the gut microbiota can induce inflammation that is associated with the pathogenesis of obesity, type 2 diabetes mellitus, and AD. The purpose of this review is to summarize and discuss the current findings that may elucidate the role of the gut microbiota in the development of AD. Understanding the underlying mechanisms may provide new insights into novel therapeutic strategies for AD.

Peptides derived from dietary proteins, have been reported to display significant antioxidant activity, which may exert notably beneficial effects in promoting human health and in food processing. Recently, much research has focused on the generation, separation, purification and identification of novel peptides from various protein sources. Some researchers have tried to discover the structural characteristics of antioxidant peptides in order to lessen or avoid the tedious and aimless work involving the ongoing generated peptide preparation schemes. This review aims to summarize the current knowledge on the relationship between the structural features of peptides and their antioxidant activities. The relationship between the structure of the precursor proteins and their abilities to release antioxidant fragments will also be summarized and inferred. The preparation methods and antioxidant capacity evaluation assays of peptides and a prediction scheme of quantitative structure-activity relationship (QSAR) will also be pointed out and discussed.

A combination of chemotherapy and photothermal therapy has emerged as a promising strategy for cancer therapy. To ensure the chemotherapeutic drug and photothermal agent could be simultaneously delivered to a tumor region to exert their synergistic effect, a safe and efficient delivery system is highly desirable. Herein, we fabricated doxorubicin (DOX) and indocyanine green (ICG) loaded poly(lactic-co-glycolic acid) (PLGA)-lecithin-polyethylene glycol (PEG) nanoparticles (DINPs) using a single-step sonication method. The DINPs exhibited good monodispersity, excellent fluorescence/size stability, and consistent spectra characteristics compared with free ICG or DOX. Moreover, the DINPs showed higher temperature response, faster DOX release under laser irradiation, and longer retention time in tumor. In the meantime, the fluorescence of DOX and ICG in DINPs was also visualized for the process of subcellular location in vitro and metabolic distribution in vivo. In comparison with chemo or photothermal treatment alone, the combined treatment of DINPs with laser irradiation synergistically induced the apoptosis and death of DOX-sensitive MCF-7 and DOX-resistant MCF-7/ADR cells, and suppressed MCF-7 and MCF-7/ADR tumor growth in vivo. Notably, no tumor recurrence was observed after only a single dose of DINPs with laser irradiation. Hence, the well-defined DINPs exhibited great potential in targeting cancer imaging and chemo-photothermal therapy.

Cancer is a severe public health issue that is a leading cause of mortality globally. It is also an impediment to improving life expectancy worldwide. Furthermore, the global burden of cancer incidence and death is continuously growing. Current therapeutic options are insufficient for patients, and tumor complexity and heterogeneity necessitate customized medicine or targeted therapy. It is critical to identify potential cancer therapeutic targets. Aberrant activation of the PI3K/AKT/mTOR pathway has a significant role in carcinogenesis. This review summarized oncogenic PI3K/Akt/mTOR pathway alterations in cancer and various cancer hallmarks associated with the PI3K/AKT/mTOR pathway, such as cell proliferation, autophagy, apoptosis, angiogenesis, epithelial-to-mesenchymal transition (EMT), and chemoresistance. Importantly, this review provided recent advances in PI3K/AKT/mTOR inhibitor research. Overall, an in-depth understanding of the association between the PI3K/AKT/mTOR pathway and tumorigenesis and the development of therapies targeting the PI3K/AKT/mTOR pathway will help make clinical decisions.

Cancer remains a highly lethal disease in the world. Currently, either conventional cancer therapies or modern immunotherapies are non-tumor-targeted therapeutic approaches that cannot accurately distinguish malignant cells from healthy ones, giving rise to multiple undesired side effects. Recent advances in nanotechnology, accompanied by our growing understanding of cancer biology and nano-bio interactions, have led to the development of a series of nanocarriers, which aim to improve the therapeutic efficacy while reducing off-target toxicity of the encapsulated anticancer agents through tumor tissue-, cell-, or organelle-specific targeting. However, the vast majority of nanocarriers do not possess hierarchical targeting capability, and their therapeutic indices are often compromised by either poor tumor accumulation, inefficient cellular internalization, or inaccurate subcellular localization. This Review outlines current and prospective strategies in the design of tumor tissue-, cell-, and organelle-targeted cancer nanomedicines, and highlights the latest progress in hierarchical targeting technologies that can dynamically integrate these three different stages of static tumor targeting to maximize therapeutic outcomes. Finally, we briefly discuss the current challenges and future opportunities for the clinical translation of cancer nanomedicines.

OBJECTIVE: To evaluate the associations between prediabetes and the risk of all cause mortality and incident cardiovascular disease in the general population and in patients with a history of atherosclerotic cardiovascular disease. DESIGN: Updated meta-analysis. DATA SOURCES: Electronic databases (PubMed, Embase, and Google Scholar) up to 25 April 2020. REVIEW METHODS: Prospective cohort studies or post hoc analysis of clinical trials were included for analysis if they reported adjusted relative risks, odds ratios, or hazard ratios of all cause mortality or cardiovascular disease for prediabetes compared with normoglycaemia. Data were extracted independently by two investigators. Random effects models were used to calculate the relative risks and 95% confidence intervals. The primary outcomes were all cause mortality and composite cardiovascular disease. The secondary outcomes were the risk of coronary heart disease and stroke. RESULTS: A total of 129 studies were included, involving 10 069 955 individuals for analysis. In the general population, prediabetes was associated with an increased risk of all cause mortality (relative risk 1.13, 95% confidence interval 1.10 to 1.17), composite cardiovascular disease (1.15, 1.11 to 1.18), coronary heart disease (1.16, 1.11 to 1.21), and stroke (1.14, 1.08 to 1.20) in a median follow-up time of 9.8 years. Compared with normoglycaemia, the absolute risk difference in prediabetes for all cause mortality, composite cardiovascular disease, coronary heart disease, and stroke was 7.36 (95% confidence interval 9.59 to 12.51), 8.75 (6.41 to 10.49), 6.59 (4.53 to 8.65), and 3.68 (2.10 to 5.26) per 10 000 person years, respectively. Impaired glucose tolerance carried a higher risk of all cause mortality, coronary heart disease, and stroke than impaired fasting glucose. In patients with atherosclerotic cardiovascular disease, prediabetes was associated with an increased risk of all cause mortality (relative risk 1.36, 95% confidence interval 1.21 to 1.54), composite cardiovascular disease (1.37, 1.23 to 1.53), and coronary heart disease (1.15, 1.02 to 1.29) in a median follow-up time of 3.2 years, but no difference was seen for the risk of stroke (1.05, 0.81 to 1.36). Compared with normoglycaemia, in patients with atherosclerotic cardiovascular disease, the absolute risk difference in prediabetes for all cause mortality, composite cardiovascular disease, coronary heart disease, and stroke was 66.19 (95% confidence interval 38.60 to 99.25), 189.77 (117.97 to 271.84), 40.62 (5.42 to 78.53), and 8.54 (32.43 to 61.45) per 10 000 person years, respectively. No significant heterogeneity was found for the risk of all outcomes seen for the different definitions of prediabetes in patients with atherosclerotic cardiovascular disease (all P>0.10). CONCLUSIONS: Results indicated that prediabetes was associated with an increased risk of all cause mortality and cardiovascular disease in the general population and in patients with atherosclerotic cardiovascular disease. Screening and appropriate management of prediabetes might contribute to primary and secondary prevention of cardiovascular disease.

Cancer immunotherapy is an innovative treatment for tumors today. In various experiments and clinical studies, it has been found that immunotherapy does have incomparable advantages over traditional anti-tumor therapy, which can prolong progression-free survival (PFS) and overall survival (OS). However, immunotherapy has obvious complexity and uncertainty. Immunotherapy may also cause severe adverse reactions due to an overactive immune system. More effective and fewer adverse reactions immunological checkpoints are still under further exploration. This review gives an overview of recent developments in immunotherapy and indicates a new direction of tumor treatment through analyzing the pros and cons of immunotherapy coupled with keeping a close watch on the development trend of the immunotherapy future.

Tuberculosis is a major health threat in many regions of the world. Opportunistic infections in immunocompromised HIV/AIDS patients and multi-drug-resistant bacterial strains have exacerbated the problem, while diagnosing tuberculosis still remains a challenge. When left undiagnosed and thus untreated, mortality rates of patients with tuberculosis are high. Standard diagnostics still rely on methods developed in the last century. They are slow and often unreliable. In an effort to reduce the burden of the disease, this paper presents our automated approach for detecting tuberculosis in conventional posteroanterior chest radiographs. We first extract the lung region using a graph cut segmentation method. For this lung region, we compute a set of texture and shape features, which enable the X-rays to be classified as normal or abnormal using a binary classifier. We measure the performance of our system on two datasets: a set collected by the tuberculosis control program of our local county's health department in the United States, and a set collected by Shenzhen Hospital, China. The proposed computer-aided diagnostic system for TB screening, which is ready for field deployment, achieves a performance that approaches the performance of human experts. We achieve an area under the ROC curve (AUC) of 87% (78.3% accuracy) for the first set, and an AUC of 90% (84% accuracy) for the second set. For the first set, we compare our system performance with the performance of radiologists. When trying not to miss any positive cases, radiologists achieve an accuracy of about 82% on this set, and their false positive rate is about half of our system's rate.

Over the past few decades, RNA sequencing has significantly progressed, becoming a paramount approach for transcriptome profiling. The revolution from bulk RNA sequencing to single-molecular, single-cell and spatial transcriptome approaches has enabled increasingly accurate, individual cell resolution incorporated with spatial information. Cancer, a major malignant and heterogeneous lethal disease, remains an enormous challenge in medical research and clinical treatment. As a vital tool, RNA sequencing has been utilized in many aspects of cancer research and therapy, including biomarker discovery and characterization of cancer heterogeneity and evolution, drug resistance, cancer immune microenvironment and immunotherapy, cancer neoantigens and so on. In this review, the latest studies on RNA sequencing technology and their applications in cancer are summarized, and future challenges and opportunities for RNA sequencing technology in cancer applications are discussed.

// Wei-Cheng Liang 1, 2 , Wei-Ming Fu 3 , Cheuk-Wa Wong 1, 2 , Yan Wang 1 , Wei-Mao Wang 1 , Guo-Xin Hu 4 , Li Zhang 1 , Li-Jia Xiao 5 , David Chi-Cheong Wan 1 , Jin-Fang Zhang 1, 6 , Mary Miu-Yee Waye 1, 2 1 School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, P.R. China 2 Croucher Laboratory for Human Genomics, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, P.R. China 3 Guangzhou Institute of Advanced Technology, Chinese Academy of Sciences, Guangzhou, P.R. China 4 Department of Infectious Diseases, Peking University Shenzhen Hospital, Shenzhen, P.R. China 5 Department of Clinical Laboratory, Nanshan Affiliated Hospital of Guangdong Medical College, Shenzhen, P.R. China 6 Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, P.R. China Correspondence to: Mary Miu-Yee Waye, e-mail: mary-waye@cuhk.edu.hk Jin-Fang Zhang, e-mail: zhangjf06@cuhk.edu.hk Keywords: miRNA sponges, lncRNA, ceRNA Received: February 05, 2015      Accepted: May 23, 2015      Published: June 05, 2015 ABSTRACT Recently, the long non-coding RNA (lncRNA) H19 has been identified as an oncogenic gene in multiple cancer types and elevated expression of H19 was tightly linked to tumorigenesis and cancer progression. However, the molecular basis for this observation has not been characterized in colorectal cancer (CRC) especially during epithelial to mesenchymal transition (EMT) progression. In our studies, H19 was characterized as a novel regulator of EMT in CRC. We found that H19 was highly expressed in mesenchymal-like cancer cells and primary CRC tissues. Stable expression of H19 significantly promotes EMT progression and accelerates in vivo and in vitro tumor growth. Furthermore, by using bioinformatics study and RNA immunoprecipitation combined with luciferase reporter assays, we demonstrated that H19 functioned as a competing endogenous RNA (ceRNA) for miR-138 and miR-200a, antagonized their functions and led to the de-repression of their endogenous targets Vimentin, ZEB1, and ZEB2, all of which were core marker genes for mesenchymal cells. Taken together, these observations imply that the lncRNA H19 modulated the expression of multiple genes involved in EMT by acting as a competing endogenous RNA, which may build up the missing link between the regulatory miRNA network and EMT progression.

The patients with high microsatellite instability (MSI-H)/mismatch repair deficient (dMMR) tumors recently have been reported that can benefit from immunotherapy, and MSI can be used as a genetic instability of a tumor detection index. However, many studies have shown that there are many heterogeneous phenomena in patients with MSI tumors in terms of immunotherapy, prognosis and chemotherapy sensitivity. Here we mainly review the research results of MSI detection methods, the mechanisms of MSI occurrence and its relationship with related tumors, aiming to make a brief analysis of the current research status of MSI and provide comparable reference and guidance value for further research in this field.

Abstract Purpose: To identify MRI-based radiomics as prognostic factors in patients with advanced nasopharyngeal carcinoma (NPC). Experimental Design: One-hundred and eighteen patients (training cohort: n = 88; validation cohort: n = 30) with advanced NPC were enrolled. A total of 970 radiomics features were extracted from T2-weighted (T2-w) and contrast-enhanced T1-weighted (CET1-w) MRI. Least absolute shrinkage and selection operator (LASSO) regression was applied to select features for progression-free survival (PFS) nomograms. Nomogram discrimination and calibration were evaluated. Associations between radiomics features and clinical data were investigated using heatmaps. Results: The radiomics signatures were significantly associated with PFS. A radiomics signature derived from joint CET1-w and T2-w images showed better prognostic performance than signatures derived from CET1-w or T2-w images alone. One radiomics nomogram combined a radiomics signature from joint CET1-w and T2-w images with the TNM staging system. This nomogram showed a significant improvement over the TNM staging system in terms of evaluating PFS in the training cohort (C-index, 0.761 vs. 0.514; P < 2.68 × 10−9). Another radiomics nomogram integrated the radiomics signature with all clinical data, and thereby outperformed a nomogram based on clinical data alone (C-index, 0.776 vs. 0.649; P < 1.60 × 10−7). Calibration curves showed good agreement. Findings were confirmed in the validation cohort. Heatmaps revealed associations between radiomics features and tumor stages. Conclusions: Multiparametric MRI-based radiomics nomograms provided improved prognostic ability in advanced NPC. These results provide an illustrative example of precision medicine and may affect treatment strategies. Clin Cancer Res; 23(15); 4259–69. ©2017 AACR.

Objective Programmed 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. Design Syngeneic 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. Results We 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 T eff 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. Conclusion Our 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.