Lung cancer is one of the most common malignant tumors, of which non-small cell lung cancer (NSCLC) accounts for about 85 %. Although immune checkpoint inhibitors (ICIs), particularly PD-1/PD-L1 inhibitors, have significantly improved the prognosis of patients with NSCLC. There are still many patients do not benefit from ICIs. Primary resistance remains a major challenge in advanced NSCLC. The cancer-immunity cycle describes the process from antigen release to T cell recognition and killing of the tumor, which provides a framework for understanding anti-tumor immunity. The classical cycle consists of seven steps, and alterations at each stage can result in resistance. This review examines the current status of PD-1/PD-L1 blockade in the treatment of advanced NSCLC and explores potential mechanisms of resistance. We summarize the latest clinical trials of PD-1/PD-L1 inhibitors combined with other therapies and explore potential targets for overcoming primary resistance to PD-1/PD-L1 inhibitors.
{"title":"Resistance to PD-1/PD-L1 immune checkpoint blockade in advanced non-small cell lung cancer","authors":"Lijun Li, Haihong Pu, Xiaoxin Zhang, Xiaotian Guo, Guangrui Li, Minghui Zhang","doi":"10.1016/j.critrevonc.2025.104683","DOIUrl":"10.1016/j.critrevonc.2025.104683","url":null,"abstract":"<div><div>Lung cancer is one of the most common malignant tumors, of which non-small cell lung cancer (NSCLC) accounts for about 85 %. Although immune checkpoint inhibitors (ICIs), particularly PD-1/PD-L1 inhibitors, have significantly improved the prognosis of patients with NSCLC. There are still many patients do not benefit from ICIs. Primary resistance remains a major challenge in advanced NSCLC. The cancer-immunity cycle describes the process from antigen release to T cell recognition and killing of the tumor, which provides a framework for understanding anti-tumor immunity. The classical cycle consists of seven steps, and alterations at each stage can result in resistance. This review examines the current status of PD-1/PD-L1 blockade in the treatment of advanced NSCLC and explores potential mechanisms of resistance. We summarize the latest clinical trials of PD-1/PD-L1 inhibitors combined with other therapies and explore potential targets for overcoming primary resistance to PD-1/PD-L1 inhibitors.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"209 ","pages":"Article 104683"},"PeriodicalIF":5.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-28DOI: 10.1016/j.critrevonc.2025.104680
Yajuan Gao , Jing He , Jing Wang , Haiou Xu , Lin Ma
Gynecologic malignancies pose a serious threat to women's health worldwide. Although immunotherapy has significantly revolutionized cancer treatment strategies, effective therapeutic options for recurrent or advanced gynecologic malignancies are still deficient, posing significant challenges to clinical therapy. Chimeric antigen receptor (CAR) T cell therapy has achieved remarkable efficacy in treating hematologic malignancies, marking a significant change in the oncology treatment paradigm. However, despite the gradual increase in CAR T cell therapy used in treating solid tumors in recent years, its efficacy in treating gynecologic malignancies still needs further validation. This review will thoroughly examine CAR-T cell engineering and its mechanism of action on specific antigens associated with gynecologic malignancies, systematically assess the current application of CAR T cell therapy in gynecologic tumors and the advancements in clinical trials, and discuss the significant challenges and corresponding strategies, thereby offering a scientific foundation and guidance for future research in this area.
{"title":"Chimeric antigen receptor T cell immunotherapy for gynecological malignancies","authors":"Yajuan Gao , Jing He , Jing Wang , Haiou Xu , Lin Ma","doi":"10.1016/j.critrevonc.2025.104680","DOIUrl":"10.1016/j.critrevonc.2025.104680","url":null,"abstract":"<div><div>Gynecologic malignancies pose a serious threat to women's health worldwide. Although immunotherapy has significantly revolutionized cancer treatment strategies, effective therapeutic options for recurrent or advanced gynecologic malignancies are still deficient, posing significant challenges to clinical therapy. Chimeric antigen receptor (CAR) T cell therapy has achieved remarkable efficacy in treating hematologic malignancies, marking a significant change in the oncology treatment paradigm. However, despite the gradual increase in CAR T cell therapy used in treating solid tumors in recent years, its efficacy in treating gynecologic malignancies still needs further validation. This review will thoroughly examine CAR-T cell engineering and its mechanism of action on specific antigens associated with gynecologic malignancies, systematically assess the current application of CAR T cell therapy in gynecologic tumors and the advancements in clinical trials, and discuss the significant challenges and corresponding strategies, thereby offering a scientific foundation and guidance for future research in this area.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"209 ","pages":"Article 104680"},"PeriodicalIF":5.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-27DOI: 10.1016/j.critrevonc.2025.104677
Chunhong Li , Jia Liao , Bo Chen , Qiang Wang
Head and neck cancer (HNC) is the sixth most common disease in the world. The recurrence rate of patients is relatively high, and the heterogeneity of tumor immune microenvironment (TIME) cells may be an important reason for this. Single-cell sequencing (SCS) is currently the most promising and mature application in cancer research. It can identify unique genes expressed in cells and study tumor heterogeneity. According to current research, the heterogeneity of immune cells has become an important factor affecting the occurrence and development of HNC. SCSs can provide effective therapeutic targets and prognostic factors for HNC patients through analyses of gene expression levels and cell heterogeneity. Therefore, this study analyzes the basic theory of HNC and the development of SCS technology, elaborating on the application of SCS technology in HNC and its potential value in identifying HNC therapeutic targets and biomarkers.
{"title":"Heterogeneity of the tumor immune cell microenvironment revealed by single-cell sequencing in head and neck cancer","authors":"Chunhong Li , Jia Liao , Bo Chen , Qiang Wang","doi":"10.1016/j.critrevonc.2025.104677","DOIUrl":"10.1016/j.critrevonc.2025.104677","url":null,"abstract":"<div><div>Head and neck cancer (HNC) is the sixth most common disease in the world. The recurrence rate of patients is relatively high, and the heterogeneity of tumor immune microenvironment (TIME) cells may be an important reason for this. Single-cell sequencing (SCS) is currently the most promising and mature application in cancer research. It can identify unique genes expressed in cells and study tumor heterogeneity. According to current research, the heterogeneity of immune cells has become an important factor affecting the occurrence and development of HNC. SCSs can provide effective therapeutic targets and prognostic factors for HNC patients through analyses of gene expression levels and cell heterogeneity. Therefore, this study analyzes the basic theory of HNC and the development of SCS technology, elaborating on the application of SCS technology in HNC and its potential value in identifying HNC therapeutic targets and biomarkers.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"209 ","pages":"Article 104677"},"PeriodicalIF":5.5,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-27DOI: 10.1016/j.critrevonc.2025.104673
Navya V.B., Ravindra Kumar
Over the years, there have been significant advancements in the field of cervical cancer research in developing new treatment approaches. One of the significant breakthroughs in cancer treatment is the emergence of immunotherapy that can be used as a standalone treatment or in combination with other cancer therapies. Immunotherapy has shown promising results in clinical trials and has become a viable strategy for treating cancer and improves the quality of life for cancer patients and overall survival rate. Here in the systematic review we are focusing towards the effectiveness and safety of immunotherapy in cervical cancer or HPV infections CIN with clinical trial data. The data extracted had from those studies were analyzed through certain statistical methods and subgroup analysis for validating and concluding our objective. PubMed and Science direct database were used for searching the studies with applied screening and filtering and 49 main reports were included for the studies. The immunotherapies subdivided to immune checkpoint inhibitors, cellular therapy and Vaccine were separately analysed through meta-analysis for the conclusion. The Pembrolizumab (immune checkpoint inhibitor), T cell therapy and Bivalent (Ecoli expressed) vaccine were analysed to be higher effective. Thus for future exploration on immunotherapy in cervical cancer, it was described in our studies of a combination of Ecoli rec HPV bivalent vaccine followed by Pembrolizumab or T cell therapy thus improving the immune mediated action against the cancer. Apart from that, a hypothetical model of multiepitope production on ecoli for vaccine generation has also been explained.
{"title":"Meta-analysis of clinical trial on the comparative efficacy and safety profiles of immunotherapeutic strategies in cervical cancer","authors":"Navya V.B., Ravindra Kumar","doi":"10.1016/j.critrevonc.2025.104673","DOIUrl":"10.1016/j.critrevonc.2025.104673","url":null,"abstract":"<div><div>Over the years, there have been significant advancements in the field of cervical cancer research in developing new treatment approaches. One of the significant breakthroughs in cancer treatment is the emergence of immunotherapy that can be used as a standalone treatment or in combination with other cancer therapies. Immunotherapy has shown promising results in clinical trials and has become a viable strategy for treating cancer and improves the quality of life for cancer patients and overall survival rate. Here in the systematic review we are focusing towards the effectiveness and safety of immunotherapy in cervical cancer or HPV infections CIN with clinical trial data. The data extracted had from those studies were analyzed through certain statistical methods and subgroup analysis for validating and concluding our objective. PubMed and Science direct database were used for searching the studies with applied screening and filtering and 49 main reports were included for the studies. The immunotherapies subdivided to immune checkpoint inhibitors, cellular therapy and Vaccine were separately analysed through meta-analysis for the conclusion. The Pembrolizumab (immune checkpoint inhibitor), T cell therapy and Bivalent (Ecoli expressed) vaccine were analysed to be higher effective. Thus for future exploration on immunotherapy in cervical cancer, it was described in our studies of a combination of Ecoli rec HPV bivalent vaccine followed by Pembrolizumab or T cell therapy thus improving the immune mediated action against the cancer. Apart from that, a hypothetical model of multiepitope production on ecoli for vaccine generation has also been explained.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"209 ","pages":"Article 104673"},"PeriodicalIF":5.5,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-25DOI: 10.1016/j.critrevonc.2025.104675
Rafael Zatti Rossetto , Sarah Franco Vieira De Oliveira Maciel , Andréia Machado Cardoso
Prostate cancer (PCa) is a complex and lethal disease in men, influenced by risk factors such as age, heredity, and lifestyle. This article reviews the roles of purinergic signaling and reactive species in PCa progression. The purinergic system involves signaling molecules, such as ATP and adenosine, specific receptors (P1 and P2), and catalytic enzymes (for example, CD39 and CD73), whose alterations contribute to cell proliferation, angiogenesis, and immune evasion. The purinergic receptors P2X7 and P2X4 modulate the prostate tumor microenvironment (TME), impacting hypoxia, apoptosis, and inflammatory pathways. Reactive oxygen species (ROS) and nitrogen species (RNS) also play crucial roles. At elevated levels, they lead to oxidative damage to DNA and mitochondria, promoting genetic instability and uncontrolled cell proliferation. These species interact with the purinergic signaling pathway, with enzymes like CD39 and CD73 playing dual roles: degrading extracellular ATP to generate immunosuppressive adenosine while simultaneously protecting against oxidative damage. This review emphasizes the dynamic interplay between inflammatory and immunosuppressive signals within the TME, mediated by ATP, ROS, and their signaling cascades. This balance determines whether the environment supports tumor progression or regression. Targeting these mechanisms through innovative therapies, including receptor inhibitors and ROS modulation, presents promising avenues for PCa treatment. Understanding the intricate roles of purinergic signaling and reactive species provides valuable insights into potential therapeutic strategies to combat PCa.
{"title":"Relationship between purinergic signalling and oxidative stress in prostate cancer: Perspectives for future therapy","authors":"Rafael Zatti Rossetto , Sarah Franco Vieira De Oliveira Maciel , Andréia Machado Cardoso","doi":"10.1016/j.critrevonc.2025.104675","DOIUrl":"10.1016/j.critrevonc.2025.104675","url":null,"abstract":"<div><div>Prostate cancer (PCa) is a complex and lethal disease in men, influenced by risk factors such as age, heredity, and lifestyle. This article reviews the roles of purinergic signaling and reactive species in PCa progression. The purinergic system involves signaling molecules, such as ATP and adenosine, specific receptors (P1 and P2), and catalytic enzymes (for example, CD39 and CD73), whose alterations contribute to cell proliferation, angiogenesis, and immune evasion. The purinergic receptors P2X7 and P2X4 modulate the prostate tumor microenvironment (TME), impacting hypoxia, apoptosis, and inflammatory pathways. Reactive oxygen species (ROS) and nitrogen species (RNS) also play crucial roles. At elevated levels, they lead to oxidative damage to DNA and mitochondria, promoting genetic instability and uncontrolled cell proliferation. These species interact with the purinergic signaling pathway, with enzymes like CD39 and CD73 playing dual roles: degrading extracellular ATP to generate immunosuppressive adenosine while simultaneously protecting against oxidative damage. This review emphasizes the dynamic interplay between inflammatory and immunosuppressive signals within the TME, mediated by ATP, ROS, and their signaling cascades. This balance determines whether the environment supports tumor progression or regression. Targeting these mechanisms through innovative therapies, including receptor inhibitors and ROS modulation, presents promising avenues for PCa treatment. Understanding the intricate roles of purinergic signaling and reactive species provides valuable insights into potential therapeutic strategies to combat PCa.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"209 ","pages":"Article 104675"},"PeriodicalIF":5.5,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-24DOI: 10.1016/j.critrevonc.2025.104674
Hui Jia , Che Bian , Yi Chang
Ferroptosis, a regulated form of cell death dependent on iron and marked by lipid peroxidation, is increasingly recognized for its role in a wide array of diseases, including cancers, neurodegenerative disorders, and tissue damage. This review examines the dynamic interaction between ferroptosis and the Wnt/β-catenin signaling pathway, focusing on how Wnt surface receptors, ligands, antagonists, and associated components influence the regulation of ferroptosis. Key elements such as Frizzled receptors, Wnt ligands, and antagonists like DKK1 are shown to affect ferroptosis by altering oxidative stress, lipid dynamics, and iron metabolism. A central aspect of this interaction is the role of the destruction complex, particularly GSK-3β, which regulates ferroptosis through its upstream modulation by the AKT pathway and downstream control over NRF2, GPX4, and SLC7A11. Furthermore, the involvement of β-catenin/TCF transcription factors in the regulation of ferroptosis emphasizes the significance of this pathway in promoting cell survival and resisting ferroptosis, particularly in various cancers. Multiple cancers, including colorectal, breast, ovarian, and lung cancers, are affected by disruptions in the Wnt/ferroptosis axis, where enhanced Wnt signaling helps cancer cells evade ferroptosis and develop resistance to treatments. Beyond cancer, this axis also plays a crucial role in neurodegenerative diseases and conditions like myocardial infarction. Additionally, natural compounds have shown potential in modulating the Wnt/ferroptosis pathway, offering promising therapeutic approaches for a variety of diseases. This review highlights the molecular mechanisms of the Wnt/ferroptosis axis, paving the way for innovative treatment options in cancer and other diseases.
{"title":"Exploring the molecular interactions between ferroptosis and the Wnt/β-catenin signaling pathway: Implications for cancer and disease therapy","authors":"Hui Jia , Che Bian , Yi Chang","doi":"10.1016/j.critrevonc.2025.104674","DOIUrl":"10.1016/j.critrevonc.2025.104674","url":null,"abstract":"<div><div>Ferroptosis, a regulated form of cell death dependent on iron and marked by lipid peroxidation, is increasingly recognized for its role in a wide array of diseases, including cancers, neurodegenerative disorders, and tissue damage. This review examines the dynamic interaction between ferroptosis and the Wnt/β-catenin signaling pathway, focusing on how Wnt surface receptors, ligands, antagonists, and associated components influence the regulation of ferroptosis. Key elements such as Frizzled receptors, Wnt ligands, and antagonists like DKK1 are shown to affect ferroptosis by altering oxidative stress, lipid dynamics, and iron metabolism. A central aspect of this interaction is the role of the destruction complex, particularly GSK-3β, which regulates ferroptosis through its upstream modulation by the AKT pathway and downstream control over NRF2, GPX4, and SLC7A11. Furthermore, the involvement of β-catenin/TCF transcription factors in the regulation of ferroptosis emphasizes the significance of this pathway in promoting cell survival and resisting ferroptosis, particularly in various cancers. Multiple cancers, including colorectal, breast, ovarian, and lung cancers, are affected by disruptions in the Wnt/ferroptosis axis, where enhanced Wnt signaling helps cancer cells evade ferroptosis and develop resistance to treatments. Beyond cancer, this axis also plays a crucial role in neurodegenerative diseases and conditions like myocardial infarction. Additionally, natural compounds have shown potential in modulating the Wnt/ferroptosis pathway, offering promising therapeutic approaches for a variety of diseases. This review highlights the molecular mechanisms of the Wnt/ferroptosis axis, paving the way for innovative treatment options in cancer and other diseases.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"210 ","pages":"Article 104674"},"PeriodicalIF":5.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oral Cancer is one of the most prevalent malignant tumors of the head and neck. The three primary clinical treatments available till now for oral cancer are chemotherapy, radiation, and surgery. The goal of this review was to outline the basic principles of immunotherapy along with various immunotherapeutic agents on Oral Squamous Cell Carcinoma.
Materials and methods
A comprehensive search in PubMed, Scopus, and Google Scholar was performed using relevant keywords. All the articles, both English as well as non-English were included also with inclusion data from high-incidence countries (South-east Asia) and the compilation was ten done after getting the data reviewed from two pathologists who were blinded to the data.
Results
All the data has been compiled and the various sections in the manuscript provides an insight into the current trends in immunotherapy.
Conclusions
Advanced research studies are needed to counteract the hurdles associated with immunotherapy so that a greater proportion of patients can be treated.
Clinical relevance
One of the more recent developments that is promising is immunotherapy, which can be quite beneficial when used as a monotherapy or an adjuvant treatment. This more recent treatment approach could serve as the fourth pillar in cancer care, alongside radiation, chemotherapy, and surgery. Because immunotherapy relies on the patient's immunological environment, careful patient selection is essential to its effectiveness.
{"title":"Immunotherapy in OSCC: Current trend and challenges","authors":"Shalini Gupta , Akanchha Singh , Sakshi Deorah , Arushi Tomar","doi":"10.1016/j.critrevonc.2025.104672","DOIUrl":"10.1016/j.critrevonc.2025.104672","url":null,"abstract":"<div><h3>Objectives</h3><div>Oral Cancer is one of the most prevalent malignant tumors of the head and neck. The three primary clinical treatments available till now for oral cancer are chemotherapy, radiation, and surgery. The goal of this review was to outline the basic principles of immunotherapy along with various immunotherapeutic agents on Oral Squamous Cell Carcinoma.</div></div><div><h3>Materials and methods</h3><div>A comprehensive search in PubMed, Scopus, and Google Scholar was performed using relevant keywords. All the articles, both English as well as non-English were included also with inclusion data from high-incidence countries (South-east Asia) and the compilation was ten done after getting the data reviewed from two pathologists who were blinded to the data.</div></div><div><h3>Results</h3><div>All the data has been compiled and the various sections in the manuscript provides an insight into the current trends in immunotherapy.</div></div><div><h3>Conclusions</h3><div>Advanced research studies are needed to counteract the hurdles associated with immunotherapy so that a greater proportion of patients can be treated.</div></div><div><h3>Clinical relevance</h3><div>One of the more recent developments that is promising is immunotherapy, which can be quite beneficial when used as a monotherapy or an adjuvant treatment. This more recent treatment approach could serve as the fourth pillar in cancer care, alongside radiation, chemotherapy, and surgery. Because immunotherapy relies on the patient's immunological environment, careful patient selection is essential to its effectiveness.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"209 ","pages":"Article 104672"},"PeriodicalIF":5.5,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143478708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-21DOI: 10.1016/j.critrevonc.2025.104657
Filippo Gagliardi , Pierfrancesco De Domenico , Silvia Snider , Francesca Roncelli , Stefano Comai , Pietro Mortini
Background
Glioblastoma (GBM) is the most aggressive primary brain tumor exhibiting extensive immune evasion mechanisms that hinder effective therapeutic interventions. This narrative review explores the immunomodulatory pathways contributing to tumor escape in GBM, specifically focusing on the role of Tryptophan (TRP) metabolism and its downstream mediators Tryptophan metabolism through the kynurenine pathway (KP) is initiated by indoleamine 2,3-dioxygenase (IDO) and tryptophan-2,3-dioxygenase (TDO2) enzymes and serves as a crucial mechanism for promoting an immunosuppressive microenvironments and systemic immunotolerance. Emerging evidence also indicates a non-enzymatic role for IDO1 signaling in these processes. The downstream effectors interact with immune cells, inducing local immunosuppression within the tumor microenvironment and altering peripheral immune responses.
Methods
We systematically reviewed databases (MEDLINE via PubMed, Science Direct, and Embase) through October 2024 to highlight the interplay between local immune escape mechanisms and circulating immunotolerance, emphasizing the role of TRP metabolic enzymes in supporting GBM progression.
Results
The literature review identified 99 records. TRP-related mechanisms play a central role in fostering immunotolerance in GBM. These phenomena involve intricate interactions between the infiltrating and circulating myeloid and lymphoid compartments, ultimately shaping a tolerant, pro-tumoral environment and the peripheral immunophenotype.
Conclusions
The biological activity of IDO1 and TRP metabolites positions these compounds as potential markers of disease activity and promising molecular targets for future therapeutic approaches.
{"title":"Immunomodulatory mechanisms driving tumor escape in glioblastoma: The central role of IDO and tryptophan metabolism in local and systemic immunotolerance","authors":"Filippo Gagliardi , Pierfrancesco De Domenico , Silvia Snider , Francesca Roncelli , Stefano Comai , Pietro Mortini","doi":"10.1016/j.critrevonc.2025.104657","DOIUrl":"10.1016/j.critrevonc.2025.104657","url":null,"abstract":"<div><h3>Background</h3><div>Glioblastoma (GBM) is the most aggressive primary brain tumor exhibiting extensive immune evasion mechanisms that hinder effective therapeutic interventions. This narrative review explores the immunomodulatory pathways contributing to tumor escape in GBM, specifically focusing on the role of Tryptophan (TRP) metabolism and its downstream mediators Tryptophan metabolism through the kynurenine pathway (KP) is initiated by indoleamine 2,3-dioxygenase (IDO) and tryptophan-2,3-dioxygenase (TDO2) enzymes and serves as a crucial mechanism for promoting an immunosuppressive microenvironments and systemic immunotolerance. Emerging evidence also indicates a non-enzymatic role for IDO1 signaling in these processes. The downstream effectors interact with immune cells, inducing local immunosuppression within the tumor microenvironment and altering peripheral immune responses.</div></div><div><h3>Methods</h3><div>We systematically reviewed databases (MEDLINE via PubMed, Science Direct, and Embase) through October 2024 to highlight the interplay between local immune escape mechanisms and circulating immunotolerance, emphasizing the role of TRP metabolic enzymes in supporting GBM progression.</div></div><div><h3>Results</h3><div>The literature review identified 99 records. TRP-related mechanisms play a central role in fostering immunotolerance in GBM. These phenomena involve intricate interactions between the infiltrating and circulating myeloid and lymphoid compartments, ultimately shaping a tolerant, pro-tumoral environment and the peripheral immunophenotype.</div></div><div><h3>Conclusions</h3><div>The biological activity of IDO1 and TRP metabolites positions these compounds as potential markers of disease activity and promising molecular targets for future therapeutic approaches.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"209 ","pages":"Article 104657"},"PeriodicalIF":5.5,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-21DOI: 10.1016/j.critrevonc.2025.104670
Shalini Gupta, Arushi Tomar, Riya Singh
Precision medicine, also known as personalised medicine, removes the limitations of "one-size-fits-all" treatment by combining genetic data with phenotypic and environmental factors to create the treatment protocols that are unique and specific for each patient. Cancer genome sequencing has made precision therapy a dream come true in this particular area. Possessing benefits of individual genetic testing over restricted generalised application of established results of NGS (Next-Generation Sequencing) for understanding pathogenetic mechanism represents a significant advancement in personalised medicine. Proteomics and RNA studies, tumour and cell-free DNA profiling using NGS, as well as a deeper comprehension of immune systems all act as contributing factors for providing better cancer treatment options. The emergence of personalised medicine is not only providing a cost- effective alternative but also promises to enhance patient survival which in turn is being facilitated by rapidly developing technologies that enable us to characterise the specific and individual molecular "nature" of a tumour. The currently available in vitro and in vivo models may be further improved by cancer organoids, which can also help us understand cancer stem cell resistance and create new cancer therapies by better cancer stem cell targeting. In this review, we examine the literature on the current function of cancer organoids in assessing therapy responses and contrast them with more conventional laboratory models like cell lines and xenografts. Therefore, this present review provides a detailed description of the current technologies as well as the limitations and future trends for the same.
{"title":"Personalized medicine in oral cancer","authors":"Shalini Gupta, Arushi Tomar, Riya Singh","doi":"10.1016/j.critrevonc.2025.104670","DOIUrl":"10.1016/j.critrevonc.2025.104670","url":null,"abstract":"<div><div>Precision medicine, also known as personalised medicine, removes the limitations of \"one-size-fits-all\" treatment by combining genetic data with phenotypic and environmental factors to create the treatment protocols that are unique and specific for each patient. Cancer genome sequencing has made precision therapy a dream come true in this particular area. Possessing benefits of individual genetic testing over restricted generalised application of established results of NGS (Next-Generation Sequencing) for understanding pathogenetic mechanism represents a significant advancement in personalised medicine. Proteomics and RNA studies, tumour and cell-free DNA profiling using NGS, as well as a deeper comprehension of immune systems all act as contributing factors for providing better cancer treatment options. The emergence of personalised medicine is not only providing a cost- effective alternative but also promises to enhance patient survival which in turn is being facilitated by rapidly developing technologies that enable us to characterise the specific and individual molecular \"nature\" of a tumour. The currently available in vitro and in vivo models may be further improved by cancer organoids, which can also help us understand cancer stem cell resistance and create new cancer therapies by better cancer stem cell targeting. In this review, we examine the literature on the current function of cancer organoids in assessing therapy responses and contrast them with more conventional laboratory models like cell lines and xenografts. Therefore, this present review provides a detailed description of the current technologies as well as the limitations and future trends for the same.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"209 ","pages":"Article 104670"},"PeriodicalIF":5.5,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143474050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-20DOI: 10.1016/j.critrevonc.2025.104661
Judit Józwiak-Hagymásy , Ábel Széles , Tamás Dóczi , Bertalan Németh , Dóra Mezei , Hédi Varga , Alessandro Gronchi , Winan J. van Houdt , Attila Tordai , Marcell Csanádi
Background
Soft tissue sarcomas (STS) are a group of solid tumors with over 50 histologic types. They account for < 1 % of new malignancies in adults and ∼2 % of cancer-related mortality. Surgery with or without radiation therapy is applied in localized STS, however, most patients develop local recurrence or metastases after surgery. This study aimed to review the literature on economic evaluations and health economic models in STS.
Methods
Systematic literature search was performed covering Medline, Embase, Scopus, Cochrane Library and PROSPERO. Searches in grey literature and snowball searches were applied. Studies were eligible if they included patients with STS, contained data on health economic evaluations, had a geographical focus on Europe or North America and were written in English. The protocol was registered in PROSPERO (ID: CRD42023483406).
Results
The review of 1638 records resulted in 22 peer-reviewed articles, 5 HTA agency documents and 2 conference posters. Among these, 19 compared pharmaceutical therapies and the remaining studies focused on diagnostics or surgery related interventions. All studies on pharmaceuticals investigated advanced STS, where patients have metastatic or locally advanced irresectable disease. Economic modelling was used in 25 studies; majority of them used the “traditional” 3-state Markov cohort or partitioned-survival modelling approach (health states: progression-free; progressed; dead).
Conclusion
Although a fairly large number of publications are available on the economic evaluation of STS, these mostly focus on a narrow patient sub-group, not eligible for surgery. The applied methodology of modelling, especially for pharmaceuticals, is mostly simplified and universally used across different jurisdictions.
{"title":"Economic evaluations and health economic models of soft tissue sarcomas: Systematic literature review from a European and North American perspective","authors":"Judit Józwiak-Hagymásy , Ábel Széles , Tamás Dóczi , Bertalan Németh , Dóra Mezei , Hédi Varga , Alessandro Gronchi , Winan J. van Houdt , Attila Tordai , Marcell Csanádi","doi":"10.1016/j.critrevonc.2025.104661","DOIUrl":"10.1016/j.critrevonc.2025.104661","url":null,"abstract":"<div><h3>Background</h3><div>Soft tissue sarcomas (STS) are a group of solid tumors with over 50 histologic types. They account for < 1 % of new malignancies in adults and ∼2 % of cancer-related mortality. Surgery with or without radiation therapy is applied in localized STS, however, most patients develop local recurrence or metastases after surgery. This study aimed to review the literature on economic evaluations and health economic models in STS.</div></div><div><h3>Methods</h3><div>Systematic literature search was performed covering Medline, Embase, Scopus, Cochrane Library and PROSPERO. Searches in grey literature and snowball searches were applied. Studies were eligible if they included patients with STS, contained data on health economic evaluations, had a geographical focus on Europe or North America and were written in English. The protocol was registered in PROSPERO (ID: CRD42023483406).</div></div><div><h3>Results</h3><div>The review of 1638 records resulted in 22 peer-reviewed articles, 5 HTA agency documents and 2 conference posters. Among these, 19 compared pharmaceutical therapies and the remaining studies focused on diagnostics or surgery related interventions. All studies on pharmaceuticals investigated advanced STS, where patients have metastatic or locally advanced irresectable disease. Economic modelling was used in 25 studies; majority of them used the “traditional” 3-state Markov cohort or partitioned-survival modelling approach (health states: progression-free; progressed; dead).</div></div><div><h3>Conclusion</h3><div>Although a fairly large number of publications are available on the economic evaluation of STS, these mostly focus on a narrow patient sub-group, not eligible for surgery. The applied methodology of modelling, especially for pharmaceuticals, is mostly simplified and universally used across different jurisdictions.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"209 ","pages":"Article 104661"},"PeriodicalIF":5.5,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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