On April 15, we interpreted 15 articles, focusing on: cancer, immunotherapy, lung cancer, tumor flora, engineered bacteria, colorectal cancer, prognosis prediction, macrophages, clinical trials, epigenetics, Exeliom, Seed Health, Haite Biotech, Danma Biotech, Heavy Pharmaceutical Group, Qifiya Technology.
The daily newspaper was published by R. AI-assisted creation generation, manual review and proofreading.
Cell: A Systematic Look at the Complexity of Cancer (Review)
Cell——[64.5]
(1) Cancer research has made tremendous progress over the past 50 years, but the "dark cloud of complexity" continues to hit the frontiers of cancer biology and cancer medicine, with sex playing a particularly prominent role in cancer susceptibility, development, and treatment response. (2) cancer-driven mutations interact with environmental or endogenous tumor promoters in cancer risk, and a variety of endogenous or lifestyle factors affect the microbiome and affect tumor occurrence and progression by stimulating other markers;(3) there are certain commonalities among cancers, all cancers are involved in the same cell cycle mechanism, exhibiting inactivation of the p53 pathway and cross-activation of Myc and PI3K pathways;(4) The cellular niche in the tumor microenvironment is made up of different cell populations, each of which may support cancer cell characteristics in different ways, thereby promoting tumor growth, invasion, and metastasis. (5) Thromboembolism is one of the main causes of death in cancer patients, and the potential susceptibility to thrombosis is related to the dysregulation of thrombo-inflammatory responses, including the interaction between coagulation and inflammatory mediators; (6) Gut microbes have different effects on immunity and cancer through a variety of different mechanisms, and targeted intervention against gut and tumor microbes is helpful for cancer treatment, blockade and prevention.
【Original Information】
Embracing cancer complexity: Hallmarks of systemic disease
2024-03-28 , Yogurt: 10.1016/J.Cell.2024.02.009
Cell: How does gut microbiota affect immunotherapy?
Cell Reports Medicine——[14.3]
(1) The interaction between microorganisms and the host immune system determines the efficacy of immune checkpoint inhibitors (ICIs), and the mechanistic pathways associated with microbiota may be the basis for anti-tumor efficacy or tumor progression effects;(2) The intestinal microbiota can be used as a biomarker for tumor prediction and prognosis, and may induce or inhibit the response of ICIs, and current studies have revealed the effects of members of taxa such as Trichonilla, Ruminococcus, Cyclolibacterium, Lactobacillus, Bacteroides, Ackermansiella, Red Bugs and Bifidobacterium on ICI;(3) The use of antibiotics and probiotics will have different effects on the efficacy of ICIs, but the application of fecal bacteria transplantation or bacterial combination drugs has shown a positive impact on the effectiveness of ICI therapy, and the mechanism mainly involves the inhibition of harmful bacteria and the activation of immune cells.
【Original Information】
Microbiome bacterial influencers of host immunity and response to immunotherapy
2024-03-21 , Doi: 10.1016/J.XCRM.2024.101487
Cell sub-journal of the domestic team: circulating microbiota DNA helps early diagnosis and recurrence prediction of lung cancer
Cell Reports Medicine——[14.3]
(1) Qiu Mantang's team from Peking University People's Hospital, Wu Hao's team from Shenzhen Second People's Hospital, and Lu Yiming's team from Beijing Institute of Radiation Medicine found that circulating microbiota DNA (cmDNA) can be used as a biomarker for early diagnosis and recurrence of lung cancer; (2) Whole genome sequencing was performed on plasma from lung cancer patients and healthy controls to identify differentially enriched microbial species; (3) A diagnostic model was developed with a sensitivity of up to 87.7% for lung cancer and an AUC value of 93.2% for the independently validated dataset ;(4) The model has 86.5% and 87.1% sensitivity for stage I lung cancer and tumors less than 1 cm in diameter, respectively;(5) the successful construction of a recurrence cmDNA model can accurately predict the recurrence of postoperative lung cancer;(6) this study highlights the significant changes in the cmDNA profile in lung cancer, indicating its potential as a biomarker for early diagnosis and recurrence.
【Original Information】
Circulating microbiome DNA as biomarkers for early diagnosis and recurrence of lung cancer
2024-03-28 , Doi: 10.1016/J.XCRM.2024.101499
Domestic team Cell sub-journal: Intratumor bacteria produce butyrate to promote lung cancer metastasis
Cell Reports Medicine——[14.3]
(1) Qiu Mantang and Li Yun from Peking University People's Hospital and Wang Jie and their team from Jiangsu Cancer Hospital found that intratumoral microbiome was associated with lung cancer recurrence, and intratumoral microbiome and circulating microbiome DNA (cmDNA) could predict cancer recurrence, and intratumor microbiome-derived butyrate promoted lung cancer metastasis;(2) Tumor tissue sequencing of lung cancer patients with recurrence or non-recurrence three years after surgery found that the intratumoral microbiome diversity in the relapsed group was low and butyrate-producing bacteria were enriched;(3) Intra-tumor microbiome characteristics and cmDNA can accurately predict lung cancer recurrence;(4) Subcutaneous injection of butyrate-producing bacterium Rossobacterium promotes subcutaneous tumor growth, migration, invasion and metastasis in mice;(5) Butyrate increases the expression of H19 in tumor cells by inhibiting HDAC2 and increasing H3K27 acetylation at the H19 promoter and inducing M2 macrophage polarization, thereby promoting lung cancer metastasis, and macrophage depletion partially eliminates the metastasis-promoting effect of butyrate.
【Original Information】
Intratumor microbiome-derived butyrate promotes lung cancer metastasis
2024-03-26 , Doi: 10.1016/J.XCRM.2024.101488
Cai Lintao/Zheng Mingbin/Chen Tingtao/Pan Hong Cell Sub-Journal: Engineered Probiotics Enhance T Cell-mediated Anti-tumor Immunity
Cell Reports——[8.8]
(1) Cai Lintao, Zheng Mingbin, Pan Hong from Shenzhen Advanced Institute and Chen Tingtao from Nanchang University published a study on the development of an engineered probiotic INP-EcN (IL-12 nanoparticle Escherichia coli Nissle1917), which biosynthesizes anti-PD-1 and releases IL-12 to initiate systemic anti-tumor immunity through T cell cascade regulation; Mechanistically, INP-EcN not only sustains the biosynthesis of anti-PD-1 to alleviate immunosuppression, but also promotes T cell activation, proliferation and infiltration through the reactive release of IL-12, thereby achieving sufficient activation threshold for immune checkpoint blockade therapy (ICB); (3) Compared with commercial inhibitors, tumor targeting and colonization of INP-EcN significantly increased local drug accumulation and significantly inhibited tumor growth and metastasis;(4) Immunoassays showed that anti-PD-1/IL-12 was CD8+A T cell-dependent manner efficiently cascades to promote antitumor effects, elucidating the immune interaction between ICB and cytokine activation.
【Original Information】
T cell cascade regulation initiates systemic antitumor immunity through living drug factory of anti-PD-1/IL-12 engineered probiotics
2024-04-09 , doi: 10.1016/j.celrep.2024.114086
Domestic team: MEX3A/circMPP6 complex promotes colorectal cancer by inhibiting autophagy
Signal Transduction and Targeted Therapy——[39.3]
(1) The team of Fengwei Wang and Dan Xie of Sun Yat-sen University and the team of VIP Qiao from Guangdong Provincial People's Hospital revealed a novel mechanism of Mex-3 RNA-binding family member A(MEX3A)/circMPP6 complex to promote the progression of colorectal cancer (CRC) by inhibiting autophagy;(2) The up-regulation of MEX3A expression in CRC tissues was associated with poor prognosis, accelerated the deterioration of CRC cells and inhibited autophagy;(3) MEX3A undergoes liquid-liquid phase separation in the cytoplasm dependent on endogenous disordered regions, and circMPP6 serves as a framework to promote the interaction between MEX3A and processing body (PBs) proteins;(4) The MEX3A/circMPP6 complex regulates the dynamics of PBs and promotes UPF-mediated degradation of phosphodiesterase 5A (PDE5A) mRNA, resulting in the invasiveness of CRC cells;(5) Clinically, CRC patients with high MEX3A expression and low PDE5A expression have the worst overall survival rate, providing a new perspective on prognostic markers and/or therapeutic targets for CRC.
【Original Information】
Mex-3 RNA binding family member A (MEX3A)/circMPP6 complex promotes colorectal cancer progression by inhibiting autophagy
2024-04-02, doi: 10.1038/s41392-024-01787-3
Nature of Nanjing Medical University: A new tool for predicting colorectal cancer survival
Nature Communications——[16.6]
(1) Meilin Wang's team at Nanjing Medical University successfully developed a colorectal cancer survival prediction tool based on pathological characteristics, genetic risk, and lifestyle, providing a new strategy for reducing colorectal cancer mortality;(2) Genome-wide survival association analysis was performed in 3703 patients to develop eight candidate polygenic prognostic scores (PPS) ;(3) In a separate cohort of 470 patients, a PPS containing 287 variants (PPS287) was identified with the best predictive performance (hazard ratio per standard deviation (HR) = 1.99, P=1.76×10-8) ;(4) PPS287 was further validated in two external cohorts with hazard ratios per standard deviation of 1.90 (P=3.21×10-14,543 patients) and 1.80 (P=1.11×10-9,713 patients, respectively) ;(5) A healthy lifestyle can reduce the adverse effects of pathological features and genetic risk, increasing the 5-year overall survival rate by 7.62% ;(6) This study confirmed the combined impact of pathological characteristics, germline variation, and lifestyle on the prognosis of colorectal cancer patients.
【Original Information】
Integration of pathologic characteristics, genetic risk and lifestyle exposure for colorectal cancer survival assessment
2024-04-08, doi: 10.1038/s41467-024-47204-9
Spatially isolated macrophage populations predict different outcomes for colon cancer
Cancer Discovery——[28.2]
(1) Five distinct human macrophage populations were identified in normal and malignant human breast and colon tissues by analyzing scRNA-seq and spatial transcriptome sequencing data, combined with immunohistochemical staining and CODEX images, (2) different macrophage populations were distributed in different microenvironmental niches and exhibited conserved cell composition, and this distribution pattern was repeated in healthy and diseased tissues, and (3) IL4I1+Macrophages engulf dead cells in regions with high cell turnover, predicting a good prognosis for colon cancer, whereas SPP1+ macrophages are enriched in hypoxic and necrotic tumor regions, predicting a poor prognosis for colon cancer;(4) A subset of FOLR2+ macrophages are embedded in the plasma cell niche, while NLRP3+ macrophages colocalize with neutrophils in tumors and activate inflammasomes therein.
【Original Information】
Spatially Segregated Macrophage Populations Predict Distinct Outcomes In Colon Cancer
2024-03-28 , Yogurt: 10.1158/2159-8290.CD-23-1300
Oxaliplatin-based adjuvant chemotherapy in older patients with stage III colon cancer: recurrence-free time was similar
Journal of Clinical Oncology——[45.3]
(1) This study analyzed the effect of adjuvant oxaliplatin-containing adjuvant chemotherapy in elderly patients on the treatment outcome of stage III colon cancer, and found that the treatment in older patients was well tolerated compared to younger patients, and the recurrence-free time was similar, indicating that the efficacy was comparable;(2) 7,909 patients were included, of which 24% were over 70 years old, and the rate of early treatment interruption was higher in older patients;(3) Diarrhea and neutropenia were more frequent in older patients treated with CAPOX, and the incidence of other grade 3 and grade 3 adverse events was similar between patients aged ≥ 70 years and < 70 years;(4) Multivariate analysis showed that there was no difference in time to recurrence between patients aged ≥ 70 years and < 70 years, but disease-free survival, overall survival, survival after recurrence, and cancer-specific survival were significantly shorter in patients aged ≥ 70 years;(5) Recurrence-free time may be a more appropriate endpoint in older patients with stage III colon cancer.
【Original Information】
Oxaliplatin-Based Adjuvant Chemotherapy in Older Patients With Stage III Colon Cancer: An ACCENT/IDEA Pooled Analysis of 12 Trials
2024-03-28 , doi: 10.1200/JCO.23.01326
Science: The poor efficacy of DNMTi in the treatment of colorectal cancer is related to EZH2-mediated H3K27me3 modification
Science Advances——[13.6]
(1) DNA methyltransferase inhibitors (DNMTi) have limited efficacy in solid tumors, and H3K27me3 modification occurs in colon cancer cells exposed to DNMTi, and this EZH2-dependent inhibitory modification has been found to limit the efficacy of DNMTi;(2) In colon cancer cells, low-dose DNMTi treatment can make them more sensitive to EZH2 inhibitors, and DNMTi-induced H3K27me3 accumulates in the gene region where EZH2 has been activated;(3) The combination of EZH2 inhibitor and DNMTi can alter the epigenetic profile to upregulate transcription of calcium-induced NFAT:AP-1 signaling pathway, and blocking this pathway will limit the transcriptional activation effect of EZH2 inhibitor and DNMTi combination, including the expression of transposable elements and innate immune response genes associated with viral defense; (4) Analysis of human primary colon cancer samples showed a positive correlation between DNMTi, innate immune response, and transcriptional signatures associated with calcium signaling. (5) i.e., compensatory EZH2 activity limits the efficacy of DNMTi in colon cancer.
【Original Information】
Select EZH2 inhibitors enhance viral mimicry effects of DNMT inhibition through a mechanism involving NFAT:AP-1 signaling
2024-03-27 , doi: 10.1126/sidev.adk4423
Exeliom initiates 3 Phase 2 clinical trials of live microbial drug EXL01
(1) On April 11, Exeliom Biosciences announced the initiation of three Phase 2 clinical trials of its live microbial drug EXL01, (2) which will evaluate the efficacy and safety of EXL01 in combination with immune checkpoint inhibitors in the treatment of gastric, non-small cell lung cancer and hepatocellular carcinoma, and (3) EXL01 is the first to use Faecalibacterium Prausnitzii) is designed to improve the response of cancer patients to immune checkpoint inhibitors to prolong survival, and (4) Exeliom Biosciences plans to share results by the end of 2026 and initiate a Phase 3 clinical trial in due course.
【Original Information】
Exeliom Biosciences announces three phase II clinical trials in immuno-oncology with lead candidate combined with immune checkpoint inhibitors
2024-04-11 , FormiWeb
Seed Health launches computational biology platform CODA for mining new probiotics
(1) On April 11, Seed Health announced the launch of CODA, a computational biology platform for the research and development of next-generation precision probiotics and microbiome health interventions; (2) the CODA platform leverages the Human Phenotype Project, the world's most comprehensive multi-omics database, led by Professor Eran Segal of the Weizmann Institute of Science, Israel; The CODA platform integrates 3 million phenotypic data from more than 13,000 individuals, combining microbiome profiling and genetic, immunological, metabolomic, and proteomic data;(4) In the future, researchers will use the CODA platform to first develop health solutions in areas such as metabolic health, brain health, menopause, and longevity.
【Original Information】
Seed Health Launches Computational Biology Platform, Powered by Most Comprehensive Host-Microbiome Data Set, to Expand Pipeline Beyond the Gut
2024-04-11 , PR Newswire
HKG-320 injection was approved for clinical trial
(1) On April 11, Wuhan Hite Biotech announced that its subsidiary HKG-320 injection had been approved by the State Food and Drug Administration for clinical trial application;(2) HKG-320 injection is a potassium competitive acid blocker used to reduce the risk of rebleeding after endoscopic treatment of upper gastrointestinal bleeding caused by acute gastric and/or duodenal ulcer in adults;(3) patients with upper gastrointestinal bleeding achieved primary hemostasis through endoscopic therapy, with an effective rate of 54%~100%, but a rebleeding rate of up to 18% , the mortality rate of rebleeding can be up to 9% ;(4) HKG-320 injection, as an antacidic agent, can overcome the limitations of intravenous proton pump inhibitors (PPIs) commonly used in clinical practice, such as slow onset, nocturnal acid breakthrough and large individual differences, and has good clinical development value.
【Original Information】
Hite Biotech: Announcement on the subsidiary's approval of drug clinical trials
2024-04-11 , Haite Biotech
The first domestic IND of Danma Biopharma's pipeline was approved
(1) Recently, the Phase 1 New Drug Application (IND) application for DM919, a pan-tumor indication checkpoint inhibitor of Danma Biologics, has been approved by the Center for Drug Evaluation (CDE) of the National Medical Products Administration of China;(2) DM919 has been officially approved by the US FDA for clinical research on December 21, 2023;(3) DM919 is a humanized monoclonal antibody targeting MICA/B protein, which is expected to be the first-in-class drug for NK/T cell checkpoint inhibitors in the world;(4) DM919 is planned to carry out multi-center, Open-label, dose-escalation, and extension clinical trial to evaluate the safety and clinical activity of DM919 in patients with advanced solid tumors.
【Original Information】
R&D News丨Danma Biotech's first pipeline was approved for IND in China
2024-04-11 , BioBAY
Sinopharm Group and Qifiya Technology launched pet health cooperation
(1) On April 10, Sinopharm Group and Qifiya Technology signed a strategic cooperation agreement at the 4th "Other Expo" in Shanghai;(2) The two parties will jointly incubate high-quality pet health products by relying on the general agency business of "Kani Baoli" products, further strengthen resource complementarity and synergy, and work together to create a broader career in the field of pet health;(3) Qifiya Technology is a company integrating R&D, production and sales of pet medical supplies, and is committed to building an ecological platform for pet services; (4) "Kani Baoli" brand pet food adoption The dual-core product concept of "two eggs and one core" will open the future of China's pet food industry with a scientific, safe and high-quality innovative dual-core process.
【Original Information】
Sinopharm Group and Qifiya Technology started a strategic cooperation in the field of pet health
2024-04-11 , 重药控股
Thanks to the reviewers of this issue: Jiu Qingchen, Yuanhuan'er, RZN, Zhang Tailiu, Richard
Click here to read the daily reports for the past 10 days:
0414 | A review of the high-scoring Cell sub-journal, an article about fermented foods
0413 | 3 major articles in the sub-journal to analyze the current situation and future of microbiome therapy
0412 | The 10 articles focus on the new achievements of the domestic team, and the research on intestinal and microbiota has blossomed in many places
0411 | Nature Today: How do colon cells work with T cells to fight off bacterial infections?
0410 | 今日Cell：首个大规模泛癌转移瘤菌群图谱重磅出炉
0409 | 高分Nature子刊：菌群产物药物研发取得新进展
0408 | 3 Million People Data: What Does "Good" Cholesterol Associate with Digestive Tract Cancer Risk?
0407 | 100分综述详解：短链脂肪酸链起饮食、菌群和免疫
0406 | Jia Wei/Liu Tiemin/Zheng Xiaojiao Cell sub-journal new discovery: improve the intestinal bacteria metabolites of depression
0405 | Gaofen Cell Sub-journal: The team of China Agricultural University explains postbiotics in detail