Cancer treatment reviews最新文献

{"title":"Non-operative management after immune checkpoint inhibitors for early-stage, dMMR/MSI-H gastrointestinal cancers","authors":"Roberta Fazio,&nbsp;Alessandro Audisio,&nbsp;Valentina Daprà,&nbsp;Chiara Conti,&nbsp;Nada Benhima,&nbsp;Fatima-Zahara Abbassi,&nbsp;Irene Assaf,&nbsp;Alain Hendlisz,&nbsp;Francesco Sclafani","doi":"10.1016/j.ctrv.2024.102752","DOIUrl":"10.1016/j.ctrv.2024.102752","url":null,"abstract":"<div><p>Surgery is a standard treatment for early-stage gastrointestinal cancers, often preceded by neoadjuvant chemo(radio)therapy or followed by adjuvant therapy. While leading to cure in a proportion of patients, it has some drawbacks such as intra/post-operative complications, mutilation and life-long functional sequelae. Further to the unprecedented efficacy data from studies of immune checkpoint inhibitors for advanced mismatch repair deficient/microsatellite instable (dMMR/MSI-H) tumours, a strong interest has recently emerged for the investigation of such agents in the neoadjuvant setting. Although limited by the exploratory design and small sample size, trials of neoadjuvant immune checkpoint inhibitors for early-stage dMMR/MSI-H gastrointestinal cancers have consistently reported complete response rates ranging from 70 % to 100 %. As a result, the question has arisen as to whether surgery is still needed or organ-preserving strategies should be offered to this especially immuno-sensitive population. In this article, we discuss the available evidence for neoadjuvant immune checkpoint inhibitors in dMMR/MSI-H gastrointestinal cancers and analyse opportunities and challenges to the implementation of non-operative management approaches in this setting.</p></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"128 ","pages":"Article 102752"},"PeriodicalIF":11.8,"publicationDate":"2024-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141053680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxicity of immunotherapy combinations with chemotherapy across tumor indications: Current knowledge and practical recommendations","authors":"Layal Rached ,&nbsp;Ariane Laparra ,&nbsp;Madona Sakkal ,&nbsp;François-Xavier Danlos ,&nbsp;Fabrice Barlesi ,&nbsp;Franck Carbonnel ,&nbsp;Eleonora De Martin ,&nbsp;Michel Ducreux ,&nbsp;Caroline Even ,&nbsp;Jerome Le Pavec ,&nbsp;Jean-Marie Michot ,&nbsp;Joana M. Ribeiro ,&nbsp;Florian Scotte ,&nbsp;Santiago Ponce Aix ,&nbsp;Olivier Lambotte ,&nbsp;Capucine Baldini ,&nbsp;Stéphane Champiat","doi":"10.1016/j.ctrv.2024.102751","DOIUrl":"https://doi.org/10.1016/j.ctrv.2024.102751","url":null,"abstract":"<div><p>Chemotherapy associated with Immune Checkpoint Inhibitors is currently the standard of care in several tumor indications. This combination approach improves progression free survival (PFS), overall survival (OS) and complete pathological response (pCR) in several cancer types both in the early and metastatic approaches. However, the distinct spectrum of toxicities between cytotoxic side effects and immune related adverse events (irAEs) with similar clinical presentations and different management strategies remains a challenge in daily practice for healthcare professionals. This review summarizes the most common toxicities reported in the randomized clinical trials that led to the subsequent FDA approval of these combinations, across tumor indications. We cite in particular: non-small cell lung cancer, small cell lung cancer, triple negative breast cancer, squamous cell carcinoma of the head and neck, gastric carcinoma, esophageal carcinoma, cervical carcinoma and biliary tract carcinoma.</p><p>We found that the combination of chemotherapy and immunotherapy was associated with an increased incidence of all grade adverse events (RR 1.11 [1.09; 1.12]) without an excess in treatment related mortality when compared to chemotherapy alone. We report also an increase in the incidence of serious adverse events (grade ≥ 3) (RR 1.16 [1.10;1.24]); in particular: high grade diarrhea, dyspnea, fatigue, rash and elevated liver enzymes.</p><p>Together with the collaboration of our institutional network of organ specialists with expertise in irAEs, we propose practical recommendations for physicians to enhance clinical care and management of patients undergoing treatment with combined ICI immunotherapy and chemotherapy.</p></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"127 ","pages":"Article 102751"},"PeriodicalIF":11.8,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140901519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neoadjuvant management of locally advanced pancreatic ductal adenocarcinoma − Heading towards a promising change in treatment paradigm","authors":"Umair Mahmood ,&nbsp;Ewa Carrier ,&nbsp;Khurum Khan","doi":"10.1016/j.ctrv.2024.102750","DOIUrl":"https://doi.org/10.1016/j.ctrv.2024.102750","url":null,"abstract":"<div><p>Traditional chemotherapy-based adjuvant therapies for locally advanced pancreatic ductal adenocarcinoma (PDAC) have been associated with poor clinical outcomes driven partly by its complex anatomy and molecular heterogeneity. Treatment for PDAC is challenged by presence of a dense tumour microenvironment involving an interplay of multiple tumoural and stromal components which promote metastatic oncogenic behaviour. PDAC also involves aberrations in multiple signalling pathways with paucity of treatment options against the most common mutations including <em>KRAS, TP53, CDKN2A</em> and<!--> <em>SMAD4</em>. However, recent discovery of new mechanisms implicated in pancreatic carcinogenesis have led to identification of promising mechanistic therapeutic targets such as <em>NET1</em> and <em>ULK1</em>. Early evidence also suggests the utility of targeting multiple DNA repair processes, modulators of DNA replication and major DNA damage response regulators. We explore the clinical rationale behind a neoadjuvant therapeutic strategy and emerging predictors of survival benefit associated with this approach. We also discuss challenges and opportunities originating from recent clinical trials evaluating neoadjuvant treatments composed of various combinations of radiotherapy, chemotherapy and immunotherapeutic regimens that have aimed to address some of these biological challenges. Selective treatment of patients harbouring specific genomic aberrations with targeted agents and immunotherapy can translate into optimum survival outcomes in PDAC. We also share perspectives on emerging prospective clinical evidence regarding stromal modifying agents, such as Tumour Growth Factor-Beta and Connective Tissue Growth Factor inhibitors along with novel vaccination-based approaches in improving PDAC outcomes.</p></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"127 ","pages":"Article 102750"},"PeriodicalIF":11.8,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140824770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Havoc in harmony: Unravelling the intricacies of angiogenesis orchestrated by the tumor microenvironment","authors":"Sushree Subhadra Acharya,&nbsp;Chanakya Nath Kundu","doi":"10.1016/j.ctrv.2024.102749","DOIUrl":"https://doi.org/10.1016/j.ctrv.2024.102749","url":null,"abstract":"<div><p>Cancer cells merely exist in isolation; rather, they exist in an intricate microenvironment composed of blood vessels, signalling molecules, immune cells, stroma, fibroblasts, and the ECM. The TME provides a setting that is favourable for the successful growth and survivance of tumors. Angiogenesis is a multifaceted process that is essential for the growth, invasion, and metastasis of tumors. TME can be visualized as a “concert hall,“ where various cellular and non-cellular factors perform in a “symphony” to orchestrate tumor angiogenesis and create “Havoc” instead of “Harmony”. In this review, we comprehensively summarized the involvement of TME in regulating tumor angiogenesis. Especially, we have focused on immune cells and their secreted factors, inflammatory cytokines and chemokines, and their role in altering the TME. We have also deciphered the crosstalk among various cell types that further aids the process of tumor angiogenesis. Additionally, we have highlighted the limitations of existing anti-angiogenic therapy and discussed various potential strategies that could be used to overcome these challenges and improve the efficacy of anti-angiogenic therapy.</p></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"127 ","pages":"Article 102749"},"PeriodicalIF":11.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140842872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Salivary toxicity from PSMA-targeted radiopharmaceuticals: What we have learned and where we are going","authors":"Miguel Muniz ,&nbsp;Charles L Loprinzi ,&nbsp;Jacob J Orme ,&nbsp;Regina M Koch ,&nbsp;Ahmed M Mahmoud ,&nbsp;Adam M Kase ,&nbsp;Irbaz B Riaz ,&nbsp;Jack R Andrews ,&nbsp;Matthew P Thorpe ,&nbsp;Geoffrey B Johnson ,&nbsp;Ayse T Kendi ,&nbsp;Eugene D Kwon ,&nbsp;Jones T Nauseef ,&nbsp;Alicia K Morgans ,&nbsp;Oliver Sartor ,&nbsp;Daniel S Childs","doi":"10.1016/j.ctrv.2024.102748","DOIUrl":"https://doi.org/10.1016/j.ctrv.2024.102748","url":null,"abstract":"<div><p>Clinical trials of prostate-specific membrane antigen (PSMA) targeted radiopharmaceuticals have shown encouraging results. Some agents, like lutetium-177 [177Lu]Lu-PSMA-617 ([¹⁷⁷Lu]Lu-PSMA-617), are already approved for late line treatment of metastatic castration-resistant prostate cancer (mCRPC). Projections are for continued growth of this treatment modality; [¹⁷⁷Lu]Lu-PSMA-617 is being studied both in earlier stages of disease and in combination with other anti-cancer therapies. Further, the drug development pipeline is deep with variations of PSMA-targeting radionuclides, including higher energy alpha particles conjugated to PSMA-honing vectors. It is safe to assume that an increasing number of patients will be exposed to PSMA-targeted radiopharmaceuticals during the course of their cancer treatment. In this setting, it is important to better understand and mitigate the most commonly encountered toxicities. One particularly vexing side effect is xerostomia. In this review, we discuss the scope of the problem, inventories to better characterize and monitor this troublesome side effect, and approaches to preserve salivary function and effectively palliate symptoms. This article aims to serve as a useful reference for prescribers of PSMA-targeted radiopharmaceuticals, while also commenting on areas of missing data and opportunities for future research.</p></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"127 ","pages":"Article 102748"},"PeriodicalIF":11.8,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140824771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment options in first-line metastatic renal carcinoma: A meta-analysis of 2556 patients treated with immune checkpoint inhibitors-based combinations in randomised controlled trials","authors":"Marcello Tucci ,&nbsp;Marta Mandarà ,&nbsp;Jacopo Giuliani ,&nbsp;Emilia Durante ,&nbsp;Consuelo Buttigliero ,&nbsp;Fabio Turco ,&nbsp;Erica Palesandro ,&nbsp;Ilaria Campisi ,&nbsp;Navdeep Singh ,&nbsp;Marco Muraro ,&nbsp;Fernando Munoz ,&nbsp;Francesco Fiorica","doi":"10.1016/j.ctrv.2024.102745","DOIUrl":"https://doi.org/10.1016/j.ctrv.2024.102745","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><p> <!-->The average five-year survival of metastatic renal cell carcinoma (mRCC) is 71%. However, there is significant variability in patient prognosis. Immune checkpoint inhibitors (ICIs) have been introduced into the treatment landscape of mRCC. This <em>meta</em>-analysis aimed to estimate progression-free and overall survival probabilities and identify possible outcome predictors of mRCC patients treated with ICI combination as first-line treatment.</p></div><div><h3>Methods</h3><p> <!-->Studies comparing the combination of ICI combinations versus standard of therapy for first-line treatment of advanced renal-cell carcinoma were searched in MEDLINE, CANCERLIT, the Cochrane Controlled Trials Register, and the Cochrane Library from inception through September 2023. Data on patient populations and outcomes were extracted from each study by three independent observers and combined using the DerSimonian and Laird methods.</p></div><div><h3>Results</h3><p> <!-->Six studies met the inclusion criteria. Globally, 5121 patients were included in this <em>meta</em>-analysis: 2556 patients treated with immune checkpoint inhibitors and 2565 with sunitinib as control. The ICI combination was associated with improved PFS (hazard ratio (HR) 0.68; 95 % confidence interval (CI), 0.56–0.81, p &lt; 0.0001). Furthermore, ICI combination was also associated with OS improvement (HR 0.85; 95 % CI, 0.78–0.92, p = 0.001). There is no statistical increase in adverse events.</p></div><div><h3>Conclusions</h3><p> <!-->Our findings show that PFS and OS are statistically increased in mRCC with ICI combination treatment by 32% and 15%, respectively.</p></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"127 ","pages":"Article 102745"},"PeriodicalIF":11.8,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140894921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Agnostic drug development revisited","authors":"Alberto Hernando-Calvo ,&nbsp;Alice Rossi ,&nbsp;Maria Vieito ,&nbsp;Emile Voest ,&nbsp;Elena Garralda","doi":"10.1016/j.ctrv.2024.102747","DOIUrl":"10.1016/j.ctrv.2024.102747","url":null,"abstract":"<div><p>The advent of molecular profiling and the generalization of next generation sequencing in oncology has enabled the identification of patients who could benefit from targeted agents. Since the tumor-agnostic approval of pembrolizumab for patients with MSI-High tumors in 2017, different molecularly-guided therapeutics have been awarded approvals and progressively incorporated in the treatment landscape across multiple tumor types. As the number of tumor-agnostic targets considered druggable expands in the clinic, novel challenges will reshape the drug development field involving all the stakeholders in oncology. In this review, we provide an overview of current tumor-agnostic approvals and discuss promising candidate therapeutics for tumor-agnostic designation and challenges for their broad implementation.</p></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"128 ","pages":"Article 102747"},"PeriodicalIF":11.8,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141066479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Pharmacological prevention and treatment of opioid-induced constipation in cancer patients: A systematic review and meta-analysis” [Cancer Treat. Rev. 125 (2024) 102704]","authors":"K.R.J. Kistemaker ,&nbsp;F. Sijani ,&nbsp;D.J. Brinkman ,&nbsp;A. de Graeff ,&nbsp;G.L. Burchell ,&nbsp;M.A.H. Steegers ,&nbsp;L. van Zuylen","doi":"10.1016/j.ctrv.2024.102738","DOIUrl":"https://doi.org/10.1016/j.ctrv.2024.102738","url":null,"abstract":"","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"127 ","pages":"Article 102738"},"PeriodicalIF":11.8,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0305737224000665/pdfft?md5=40774cc406deb9739598f28eb949855b&pid=1-s2.0-S0305737224000665-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140807159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intratumoral therapies in head and neck squamous cell carcinoma: A systematic review and future perspectives","authors":"Pablo Jiménez-Labaig ,&nbsp;Antonio Rullan ,&nbsp;Irene Braña ,&nbsp;Alberto Hernando-Calvo ,&nbsp;Victor Moreno ,&nbsp;Bernard Doger ,&nbsp;George Bitar ,&nbsp;Derfel Ap Dafydd ,&nbsp;Alan Melcher ,&nbsp;Kevin J. Harrington","doi":"10.1016/j.ctrv.2024.102746","DOIUrl":"https://doi.org/10.1016/j.ctrv.2024.102746","url":null,"abstract":"<div><h3>Background</h3><p>Head and neck squamous cell carcinoma (HNSCC) presents an ideal scenario for intratumoral therapies (IT), due to its local recurrence pattern and frequent superficial extension. IT therapies aim to effect tumor regression by directly injecting antineoplastic agents into lesions. However, there is a lack of updated evidence regarding IT therapies in HNSCC.</p></div><div><h3>Patients and methods</h3><p>A systematic literature search (CRD42023462291) was conducted using WebOfScience, <span>ClinicalTrials.gov</span><svg><path></path></svg>, and conference abstracts from ESMO and ASCO, identifying for IT clinical trials in patients with HNSCC, from database creation to September 12th, 2023. Efficacy as well as safety (grade ≥ 3 treatment-related adverse events[trAEs]) were reported.</p></div><div><h3>Results</h3><p>After evaluation of 1180 articles identified by the systematic search, 31 studies treating 948 patients were included. IT injectables were categorized as chemotherapies with or without electroporation (k = 4, N = 268), oncolytic viruses, plasmids, and bacteria-based (k = 16, N = 446), immunotherapies and EGFR-based therapies (k = 5, N = 160), radioenhancer particles (k = 2, N = 68), and calcium electroporation (k = 1, n = 6). EGFR-antisense plasmids, NBTXR3 radioenhancer and immune innate agonists show best overall response rates, at 83 %, 81 % and 44 % respectively. Eleven (35 %) studies added systemic therapy or radiotherapy to the IT injections. No study used predictive biomarkers to guide patient selection. 97 % studies were phase I-II. Safety-wise, electroporation and epinephrine-based injectable trials had significant local symptoms such as necrosis, fistula formation and post-injection dysphagia. Treatment-related tumor haemorrhages of various grades were described in several trials. Grade ≥ 3 trAEs attributable to the other therapies mainly comprised general symptoms such as fatigue. There were 3 injectable-related deaths across the systematic review.</p></div><div><h3>Conclusion</h3><p>This is the first review to summarize all available evidence of IT in HNSCC. As of today, IT therapies lack sufficient evidence to recommend their use in clinical practice. Continuing research on potential molecules, patient selection, safe administration of injections and controlled randomized trials are needed to assess their added benefit.</p></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"127 ","pages":"Article 102746"},"PeriodicalIF":11.8,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140816718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The tumor immune composition of mismatch repair deficient and Epstein-Barr virus-positive gastric cancer: A systematic review","authors":"J. Bos ,&nbsp;T.S. Groen-van Schooten ,&nbsp;C.P. Brugman ,&nbsp;F.S. Jamaludin ,&nbsp;H.W.M. van Laarhoven ,&nbsp;S. Derks","doi":"10.1016/j.ctrv.2024.102737","DOIUrl":"https://doi.org/10.1016/j.ctrv.2024.102737","url":null,"abstract":"<div><h3>Background</h3><p>Gastric cancer (GC), known for its unfavorable prognosis, has been classified in four distinct molecular subtypes. These subtypes not only exhibit differences in their genome and transcriptome but also in the composition of their tumor immune microenvironment. The microsatellite instable (MSI) and Epstein-Barr virus (EBV) positive GC subtypes show clear clinical benefits from immune checkpoint blockade, likely due to a neoantigen-driven and virus-driven antitumor immune response and high expression of immune checkpoint molecule PD-L1. However, even within these subtypes response to checkpoint inhibition is variable, which is potentially related to heterogeneity in the tumor immune microenvironment (TIME) and expression of co-inhibitory molecules. We conducted a systematic review to outline the current knowledge about the immunological features on the TIME of MSI and EBV + GCs.</p></div><div><h3>Methods</h3><p>A systematic search was performed in PubMed, EMBASE and Cochrane Library. All articles from the year 1990 and onwards addressing immune features of gastric adenocarcinoma were reviewed and included based on predefined in- and exclusion criteria.</p></div><div><h3>Results</h3><p>In total 5962 records were screened, of which 139 were included that reported immunological data on molecular GC subtypes. MSI and EBV + GCs were reported to have a more inflamed TIME compared to non-MSI and EBV- GC subtypes. Compared to microsatellite stable (MSS) tumors, MSI tumors were characterized by higher numbers of CD8 + and FoxP3 + T cells, and tumor infiltrating pro- and anti-inflammatory macrophages. HLA-deficiency was most common in MSI tumors compared to other molecular GC subtypes and associated with lower T and B cell infiltrates compared to HLA-proficient tumors. EBV + was associated with a high number of CD8 + T cells, Tregs, NK cells and macrophages. Expression of PD-L1, CTLA-4, Granzyme A and B, Perforin and interferon-gamma was enriched in EBV + tumors. Overall, MSI tumors harbored a more heterogeneous TIME in terms of immune cell composition and immune checkpoints compared to the EBV + tumors.</p></div><div><h3>Discussion and conclusion</h3><p>MSI and EBV + GCs are highly <em>Handbook for Conducting a Literature-Based Health Assessment Using OHAT Approach for Systematic Review and Evidence Integration</em>.; 2019pro-inflammatory immune cell populations. Although studies on the direct comparison of EBV + and MSI tumors are limited, EBV + tumors show less intra-subgroup heterogeneity compared to MSI tumors. More studies are needed to identify how Intra-subgroup heterogeneity impacts response to immunotherapy efficacy.</p></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"127 ","pages":"Article 102737"},"PeriodicalIF":11.8,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0305737224000641/pdfft?md5=cf5fafa8f781a9a9ae69668d279d64b7&pid=1-s2.0-S0305737224000641-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140650665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}