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Cancer Biology & Medicine 2024年第1期21卷 65-82页

作者： Sen Wang Benling Xu Yangyang Zhang Guangyu Chen Peng Zhao Quanli Gao Long Yuan department of Gastrointestinal Surgery Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhou 450003China department of immunotherapy Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhou 450003China

Intestinal flora affects the maturation of the host immune system,serves as a biomarker and efficacy predictor in the immunotherapy of several cancers,and has an important role in the development of colorectal cancer(CRC).Anti-PD-1/PD-L1 antibodies have shown satisfactory results in MSI-H/d MMR CRC but performed poorly in patients with MSS/p MMR *** recent years an increasing number of studies have shown that intestinal flora has an important impact on anti-PD-1/PD-L1 antibody efficacy in CRC *** and clinical evidence have suggested that anti-PD-1/PD-L1 antibody efficacy can be improved by altering the composition of the intestinal flora in ***,we summarize the studies related to the influence of intestinal flora on anti-PD-1/PD-L1 antibody efficacy in CRC and discuss the potential underlying mechanism(s).We have focused on the impact of the intestinal flora on the efficacy and safety of anti-PD-1/PD-L1 antibodies in CRC and how to better utilize the intestinal flora as an adjuvant to improve the efficacy of anti-PD-1/PD-L1 *** addition,we have provided a basis for the potential of the intestinal flora as a new treatment modality and indicator for determining patient prognosis.

关键词： Intestinal flora anti-PD-1/PD-L1 therapy colorectal cancer immune checkpoint inhibitor CD8~+T cell

Hepatic vein reconstruction during hepatectomy:A feasible and underused technique

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 421-427页

作者： Manish Ahuja Kunal Joshi Chris Coldham Paulo Muiesan Bobby Dasari Manuel Abradelo Ravi Marudanayagam Darius Mirza John Isaac David Bartlett Nikolaos A Chatzizacharias Robert P Sutcliffe Keith J Roberts department of HPB and Liver Transplant Surgery University Hospitals Birmingham NHS Foundation TrustBirminghamUK Institute of Immunology and immunotherapy University of BirminghamBirminghamUK

Complete surgical resection(R0)of liver tumors,primary or metastatic,remains the main objective in management of primary and metastatic liver tumors[1].Tumors invading to the proximity of the hepatic venous outflow pose a peculiar challenge to achieve R0 resections,because this location may render a tumor *** median survival of patients with liver tumor without surgery is less than 12 months[2].Even with surgery,post-hepatectomy liver failure and subsequently increased mortality are the main problems associated with complex resection[3].Moreover,when the vein is affected,vein resection and subsequent reconstruction are *** resection is a standard practice in liver resection and transplantation[4],for example,hepatic vein reconstruction during a living-donor liver transplant,porto-mesenteric axis reconstruction during resection of advanced pancreatic cancer and caval reconstruction during resection of retroperitoneal ***,novel techniques like total hepatic vascular exclusion(HVE)[5],veno-venous bypass[6]and ex vivo hepatic resection[7,8]have facilitated curative resections of tumors close to one or more major hepatic veins.

关键词： hepatectomy surgery mortality

Navigating reflux disease after achalasia treatments:Balancing risks and benefits

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World Journal of Gastroenterology 2024年第21期30卷 2740-2743页

作者： Ewen A Griffiths Enoch Wong department of Upper Gastrointestinal Surgery University Hospitals Birmingham NHS Foundation TrustBirmingham B152GWWest MidlandsUnited Kingdom department of Immunology and immunotherapy University of BirminghamBirmingham B152TTWest MidlandsUnited Kingdom

The peroral endoscopic myotomy(POEM)procedure has revolutionized the management of achalasia in many centres around the world as it offers patients a minimally invasive endoscopic solution to their dysphagia caused by *** its success in alleviating dysphagia,concerns regarding postoperative gastroesophageal reflux disease have emerged as a pertinent issue which are not fully *** this study,Nabi et al have comprehensively reviewed the topic of the prediction,prevention and management of gastroesophageal reflux after *** is a purely endoscopic procedure which is usually performed without any anti-reflux *** patients may be better served by a laparoscopic Heller’s myotomy and fundoplication and it is important that gastroenterologists and surgeons provide comprehensive risks and benefits of each achalasia treatment option so that patients can decide what treatment is best for *** article by Nabi et al provides a comprehensive review of the current status of this issue to allow these discussions to occur.

关键词： Achalasia Gastro-esophageal reflux disease Laparoscopic heller’s myotomy Peroral endoscopic myotomy Fundoplication

The immune system: uncharted pathways between senses and the brain

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Neural Regeneration Research 2024年第6期19卷 1173-1174页

作者： Noelia Casares Mar Cuadrado-Tejedor Ana García-Osta Juan José Lasarte Immunology and immunotherapy Program Centre for Applied Medical Research (CIMA) University of NavarraIDISNA Division of Gene Therapy for Neurological Disorders Centre for Applied Medical Research (CIMA) University of NavarraIDISNA Pathology Anatomy and Physiology Department School of Medicine University of NavarraIDISNA

Humans and animals use the classic five senses-sight, hearing, touch, smell, and taste-to detect and monitor their environment, with the sense of position and movement often referred to as the sixth sense. The perception of external signals through the senses is essential to an organism’s survival, transmitting signals to the central nervous system(CNS) and prompting physiological changes in other biological systems. In addition to the direct effects of sense-induced mediators in the brain,

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Evaluation of the safety and efficiency of cytotoxic T cell therapy sensitized by tumor antigens original from T-ALL-iPSC in vivo

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Cancer Innovation 2024年第1期3卷 50-60页

作者： Weiran Li Meiling Zhou Lu Wang Liying Huang Xuemei Chen Xizhuo Sun Tao Liu department of Tumor immunotherapy Shenzhen Luohu People's HospitalThe Third Affiliated Hospital of Shenzhen UniversityShenzhenGuangdongChina Cell Quality Testing Laboratory of Shenzhen Luohu Hospital Group ShenzhenGuangdongChina

Background:Since RNA sequencing has shown that induced pluripotent stem cells(iPSCs)share a common antigen profile with tumor cells,cancer vaccines that focus on iPSCs have made promising progress in recent ***,we showed that iPSCs derived from leukemic cells of patients with primary T cell acute lymphoblastic leukemia(T-ALL)have a gene expression profile similar to that of T-ALL cell ***:Mice with T-ALL were treated with dendritic and T(DC-T)cells loaded with intact and complete antigens from T-ALL-derived iPSCs(T-ALL-iPSCs).We evaluated the safety and antitumor efficiency of autologous tumor-derived iPSC antigens by flow cytometry,cytokine release assay,acute toxicity experiments,long-term toxicity experiments,and other ***:Our results indicate that complete tumor antigens from T-ALL-iPSCs could inhibit the growth of inoculated tumors in immunocompromised mice without causing acute and long-term ***:T-ALL-iPSC-based treatment is safe and can be used as a potential strategy for leukemia immunotherapy.

关键词： adoptive cell therapy drug safety evaluation IPSCs T-ALL

Revolutionizing tumor immunotherapy:unleashing the power of progenitor exhausted T cells

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Cancer Biology & Medicine 2024年第6期21卷 499-512页

作者： Zhang Fang Xinyi Ding Hao Huang Hongwei Jiang Jingting Jiang Xiao Zheng department of Tumor Biological Treatment The Third Affiliated Hospital of Soochow UniversityChangzhou 213003China Jiangsu Engineering Research Center for Tumor immunotherapy The Third Affiliated Hospital of Soochow UniversityChangzhou 213003China Institute for Cell Therapy of Soochow University The Third Affiliated Hospital of Soochow UniversityChangzhou 213003China

In exploring persistent infections and malignancies, a distinctive subgroup of CD8^(+) T cells, progenitor exhausted CD8^(+) T(Tpex) cells, has been identified. These Tpex cells are notable for their remarkable self-renewal and rapid proliferation abilities. Recent strides in immunotherapy have demonstrated that Tpex cells expand and differentiate into responsive exhausted CD8^(+) T cells, thus underscoring their critical role in the immunotherapeutic retort. Clinical examinations have further clarified a robust positive correlation between the proportional abundance of Tpex cells and enhanced clinical prognosis. Tpex cells have found noteworthy applications in the formulation of inventive immunotherapeutic approaches against tumors. This review describes the functions of Tpex cells in the tumor milieu, particularly their potential utility in tumor immunotherapy. Precisely directing Tpex cells may be essential to achieving successful outcomes in immunotherapy against tumors.

关键词： Progenitor exhausted CD8^(+)T cells TCF-1 immunotherapy tumor microenvironment cellular crosstalk

Recent advances in cancer-associated fibroblast:Biomarkers,signaling pathways,and therapeutic opportunities

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Chinese Medical Journal 2024年第6期137卷 638-650页

作者： Donger Zhou Lei Zheng department of Hepatobiliary-Pancreatic Surgery The Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Sidney Kimmel Comprehensive Cancer Center The Skip Viragh Pancreatic Cancer Center for Clinical Research and Careand The Bloomberg-Kimmel Institute for Immunotherapy at Johns Hopkins University School of MedicineBaltimoreMD 21287USA

Anti-cancer therapies usually focus on tumor cells,but non-tumor stromal components in the tumor microenvironment also play vital roles in tumor initiation and progression,which may be the prognostic factors and potential therapeutic ***-associated fibroblasts(CAFs)are the essential component in the tumor environment,exhibiting high heterogeneity in their cell origin and phenotype with diverse functions that influence tumor angiogenesis,immune systems,and ***-cell RNA sequencing and genetically engineered mouse models have increased our understanding of CAF diversity,and many subtypes have been ***,the precise functions of these subtypes need to be studied and *** of signaling pathways and epigenetic changes in CAFs facilitate understanding of the phenotypes of CAFs and the crosstalk between tumor cells and CAFs to provide potential therapeutic *** clinical trials,including phase III trials targeting CAFs,have been performed ***,few of these trials have generated promising results,which indicates that the complexity of CAFs in the tumor microenvironment remains largely unknown,and in-depth investigations of CAFs should be *** review summarizes the research on CAFs,focusing on the heterogeneity of their phenotypes and functions,specific signaling pathways,and the therapeutic strategies involving ***,we briefly discuss the current technologies commonly used in CAF studies and describe the challenges and future perspectives of CAF research.

关键词： Cancer-associated fibroblasts Tumor microenvironment Anti-cancer therapy Targeted therapy

O_(2)-generating multifunctional polymeric micelles for highly efficient and selective photodynamic-photothermal therapy in melanoma

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Chinese Chemical Letters 2024年第7期35卷 394-399页

作者： Yu Qin Mingyang Huang Chenlu Huang Hannah LPerry Linhua Zhang Dunwan Zhu Tianjin Key Laboratory of Biomedical Materials Key Laboratory of Biomaterials and Nanotechnology for Cancer ImmunotherapyInstitute of Biomedical EngineeringChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300192China Molecular Sciences Research Hub Department of ChemistryWhite City CampusImperial College LondonLondon W120BZUnited Kingdom

Photothermal therapy(PTT)and photodynamic therapy(PDT)have received tremendous attention owing to their great potential for tumor ***,two main issues hamper the antitumor performance of PDT:overexpression of glutathione(GSH)in tumors,which consumes PDT-induced reactive oxygen species(ROS),and hypoxia within the tumor *** drawbacks of PTT include uneven temperature distribution and the upregulation of the heat-shock proteins in tumors,both of which result in ineffective *** address these issues,a MnO_(2)doped nano-delivery system(HTIM-PMs)was synthesized by one-step self-assembly of disulfide bond bridged copolymers for indocyanine green(ICG)and MnO_(2)*** surface of polymeric micelles was layered with hyaluronan(HA)and transactivator(TAT)peptides to improve active targeting and increase cell *** internalization,HTIM-PMs showed responsiveness to the tumor microenvironment(acid pH,high glutathione,high H_(2)O_(2)).Breaking the disulfide bond reduced the intratumoral GSH level and simultaneously released the MnO_(2)and *** released MnO_(2)further reduced the GSH level and promoted O_(2)generation,thus enhancing the PDT *** PTT-mediated hyperthermia accelerated blood flow,which is beneficial for O_(2)distribution,and promotes ROS *** PTT-mediated adjuvant effects further overcame the limitations of PDT and the robust PDT effect in turn compensated for the deficiency of *** promising platform exhibited a significant improvement in the PTT-PDT cancer treatment strategy compared to previously reported nanostructures.

关键词： Photodynamic therapy Photothermal therapy Oxygen generating One-step self-assembly Stimuli-responsive nanoparticles

HIF-1α signaling: Essential roles in tumorigenesis and implications in targeted therapies

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Genes & Diseases 2024年第1期11卷 234-251页

作者： Yan Zhao Cheng Xing Yating Deng Can Ye Hongling Peng department of Hematology The Second Xiangya HospitalCentral South UniversityChangshaHunan 410011China Hunan Key Laboratory of Tumor Models and Individualized Medicine The Second Xiangya HospitalCentral South UniversityChangshaHunan 410011China Hunan Engineering Research Center of Cell immunotherapy for Hematopoietic Malignancies The Second Xiangya HospitalCentral South UniversityChangshaHunan 410011China

The hypoxic microenvironment is an essential characteristic of most malignant ***,hypoxia-inducible factor-1 alpha(HIF-1a)is a key regulatory factor of cellular adaptation to hypoxia,and many critical pathways are correlated with the biological activity of organisms via *** the intra-tumoral hypoxic environment,HIF-1αis highly expressed and contributes to the malignant progression of tumors,which in turn results in a poor prog-nosis in ***,it has been indicated that HiF-1αinvolves in various critical pro-cesses of life events and tumor development via regulating the expression of HiF-1a target genes,such as cell proliferation and apoptosis,angiogenesis,glucose metabolism,immune response,therapeutic resistance,*** from solid tumors,accumulating evidence has re-vealed that HiF-1αis also closely associated with the development and progression of hemato-logical malignancies,such as leukemia,lymphoma,and multiple *** inhibition of HiF-1a can facilitate an increased sensitivity of patients with malignancies to relevant ther-apeutic *** the review,we elaborated on the basic structure and biological functions of HIF-1a and summarized their current role in various *** is expected that they will have future potential fortargeted therapy.

关键词： Angiogenesis Hematological malignancies Hypoxia-inducible factor-1 alpha(HIF-1α) Immune escape Targeted therapy

The RNA m^(6)A demethylase ALKBH5 drives emergency granulopoiesis and neutrophil mobilization by upregulating G-CSFR expression

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Cellular & Molecular Immunology 2024年第1期21卷 6-18页

作者： Yang Liu Renjie Song Zhike Lu Lu Zhao Xinyi Zhan Yini Li Xuetao Cao department of Immunology Center for ImmunotherapyInstitute of Basic Medical SciencesPeking Union Medical CollegeChinese Academy of Medical SciencesBeijingChina Suzhou Institute of Systems Medicine Chinese Academy of Medical SciencesSuzhouChina Frontier Research Center for Cell Response Institute of ImmunologyCollege of Life SciencesNankai UniversityTianjinChina School of Life Sciences Westlake UniversityHangzhouChina

Emergency granulopoiesis and neutrophil mobilization that can be triggered by granulocyte colony-stimulating factor(G-CSF)through its receptor G-CSFR are essential for antibacterial innate ***,the epigenetic modifiers crucial for intrinsically regulating G-CSFR expression and the antibacterial response of neutrophils remain largely unclear.N6-methyladenosine(m^(6)A)RNA modification and the related demethylase alkB homolog 5(ALKBH5)are key epigenetic regulators of immunity and inflammation,but their roles in neutrophil production and mobilization are still *** used cecal ligation and puncture(CLP)-induced polymicrobial sepsis to model systemic bacterial infection,and we report that ALKBH5 is required for emergency granulopoiesis and neutrophil ***5 depletion significantly impaired the production of immature neutrophils in the bone marrow of septic *** addition,Alkbh5-deficient septic mice exhibited higher retention of mature neutrophils in the bone marrow and defective neutrophil release into the circulation,which led to fewer neutrophils at the infection site than in their wild-type *** bacterial infection,ALKBH5 imprinted production-and mobilization-promoting transcriptome signatures in both mouse and human ***,ALKBH5 erased m^(6)A methylation on the CSF3R mRNA to increase the mRNA stability and protein expression of G-CSFR,consequently upregulating cell surface G-CSFR expression and downstream STAT3 signaling in *** RIP-qPCR results confirmed the direct binding of ALKBH5 to the CSF3R mRNA,and the binding strength declined upon bacterial infection,accounting for the decrease in G-CSFR expression on bacteria-infected *** these results collectively,we define a new role of ALKBH5 in intrinsically driving neutrophil production and mobilization through m^(6)A demethylation-dependent posttranscriptional regulation,indicating that m^(6)A RNA modification in neutrop

关键词： Emergency granulopoiesis Neutrophil mobilization ALKBH5 m^(6)A RNA modification G-CSF receptor