Critical reviews in oncology/hematology最新文献

{"title":"Exploring the role of TERT in thyroid Cancer: A systematic review","authors":"Thais Maloberti ,&nbsp;Andrea Repaci ,&nbsp;Laura Poppi ,&nbsp;Floriana Jessica Di Paola ,&nbsp;Giulia Calafato ,&nbsp;Sara Coluccelli ,&nbsp;Francesca Carosi ,&nbsp;Alessandra Colapinto ,&nbsp;Simone Colombero ,&nbsp;Giacomo Credi ,&nbsp;Giovanni Tallini ,&nbsp;Maria A. Pantaleo ,&nbsp;Margherita Nannini ,&nbsp;Dario de Biase","doi":"10.1016/j.critrevonc.2025.104792","DOIUrl":"10.1016/j.critrevonc.2025.104792","url":null,"abstract":"<div><h3>Background</h3><div><em>TERT</em> gene mutations play critical roles in tumor progression and have important implications in several solid tumors, including thyroid carcinoma. This study aimed to evaluate the association between <em>TERT</em> promoter mutations and histology and clinical features of thyroid carcinoma (TC).</div></div><div><h3>Materials and methods</h3><div>We performed an up-to-date systematic review and a comprehensive meta-analysis. Systematic searches were made on MEDLINE (via Pubmed) databases using relevant keywords, and articles published until November 1st, 2024 were selected. A total of 54 studies and 17’021 samples are included in the meta-analysis. Relevant data for the meta-analysis was extracted, and for statistical analysis, chi-square calculation was used.</div></div><div><h3>Results</h3><div>Thyroid carcinomas with the highest frequency of <em>TERT</em> mutations are Anaplastic thyroid carcinoma (55.8 %) and Diffuse sclerosing variant of papillary thyroid carcinoma (60.4 %). No <em>TERT</em> mutations founds in Benign neoplasm, NIFTP and Medullary thyroid carcinoma. Mutations with the highest frequency is c.–124C&gt;T (chr5:1295228 - C228T). <em>TERT</em> mutations are statistically correlated with Stage III&amp;IV, presence of metastasis, overall survival, recurrence and radioiodine-refractory.</div></div><div><h3>Conclusion</h3><div><em>TERT</em> mutation plays a crucial role as a prognostic biomarker with tumor aggressiveness. Thus, in clinical practice, mutational status assessment of the <em>TERT</em> promoter should be considered for accurate prognostic stratification of TCs.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"213 ","pages":"Article 104792"},"PeriodicalIF":5.5,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251329","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}

{"title":"The evolving landscape of hormone receptor-positive/HER2-negative metastatic breast cancer (EVOLVE): An Italian Delphi consensus report","authors":"Federica Miglietta ,&nbsp;Maria Grazia Razeti ,&nbsp;Aldo Caltavituro ,&nbsp;Arianna Dri ,&nbsp;Carmine Valenza ,&nbsp;Giampaolo Bianchini ,&nbsp;Laura Biganzoli ,&nbsp;Andrea Botticelli ,&nbsp;Michele Caruso ,&nbsp;Saverio Cinieri ,&nbsp;Carmen Criscitiello ,&nbsp;Carmine De Angelis ,&nbsp;Michelino De Laurentis ,&nbsp;Lucia Del Mastro ,&nbsp;Sabino De Placido ,&nbsp;Marzia Del Re ,&nbsp;Maria Vittoria Dieci ,&nbsp;Alessandra Fabi ,&nbsp;Daniele Generali ,&nbsp;Alessandra Gennari ,&nbsp;Grazia Arpino","doi":"10.1016/j.critrevonc.2025.104793","DOIUrl":"10.1016/j.critrevonc.2025.104793","url":null,"abstract":"<div><h3>Background</h3><div>The expanding treatment landscape for patients with hormone receptor-positive, HER2-negative (HR+/HER2-) metastatic breast cancer (mBC) has led to the emergence of new \"grey areas\" not covered by international guidelines, where treatment decision making is particularly challenging.</div></div><div><h3>Methods</h3><div>Sixteen relevant statements regarding the management of HR+ /HER2- mBC were formulated by an Executive Board and validated by a Scientific Board, composed by internationally recognized experts in the field of BC. Subsequently, 50 Italian oncologists were surveyed between May 2024 and June 2024 through the modified Delphi method, in order to capture their rate of agreement and disagreement on the proposed statements.</div></div><div><h3>Results</h3><div>The consensus was reached for all 16 statements: 4 were related to resistance and sensitivity to CDK4/6 inhibitors and endocrine therapy, 6 to biomarkers for HR+ /HER2- mBC, and 6 to treatment algorithm of HR+ /HER2- mBC. The Panel critically and comprehensively discussed the most relevant results, especially regarding the statements with lower level of agreement (which ranged from 85.4 % to 100 %).</div></div><div><h3>Conclusions</h3><div>The treatment of HR+ /HER2- mBC is currently being reshaped due to the expansion of its pharmacopoeia, the better understanding of its molecular determinants and the validation of biomarkers for patient selection. This consensus addressed the most controversial questions related to treatment decision and reached the agreement in all statements.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"213 ","pages":"Article 104793"},"PeriodicalIF":5.5,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251331","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}

{"title":"The role of miR-429 in cancer: From biogenesis, signaling pathways, interactions with long non-coding RNAs, and function to therapeutic application","authors":"Ensiyeh Bahadoran ,&nbsp;Abouzar Babaei ,&nbsp;Reza Ranji ,&nbsp;Parisa Badameh ,&nbsp;Samira Sabzi ,&nbsp;Babak Rahmani ,&nbsp;Hadi Ebadi","doi":"10.1016/j.critrevonc.2025.104795","DOIUrl":"10.1016/j.critrevonc.2025.104795","url":null,"abstract":"<div><div>MicroRNAs (miRNAs) have emerged as critical regulators of gene expression, playing pivotal roles in cancer biology. Among these, miR-429, a member of the miR-200 family, influences migration, metastasis, apoptosis, and cell proliferation, all of which are vital for controlling cancer biology. This review examined the biogenesis, regulation, and signaling pathways associated with miR-429, as well as its interactions with long non-coding RNAs (lncRNAs) and other molecular networks that contribute to tumorigenesis. We explore its diverse expression patterns across various malignancies, including renal cell carcinoma, esophageal cancer, breast cancer, lung cancer, and glioblastoma, highlighting its dual role in tumorigenesis and metastasis. Additionally, it addresses the clinical relevance of miR-429, assessing its potential as a biomarker for cancer diagnosis, prognosis, and its promising therapeutic implications. Through a detailed analysis of miR-429 expression patterns and their impact across different cancer types, this review highlights its complex mechanisms in different cancers and its potential for targeted cancer therapy.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"213 ","pages":"Article 104795"},"PeriodicalIF":5.5,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144230207","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}

{"title":"The role of ATF3 in the crosstalk between cellular stress response and ferroptosis in tumors","authors":"Mingbo Jia ,&nbsp;Minghao Shi ,&nbsp;Yao Zhao ,&nbsp;Yao Li ,&nbsp;Xiaoyi Liu ,&nbsp;Liyan Zhao","doi":"10.1016/j.critrevonc.2025.104791","DOIUrl":"10.1016/j.critrevonc.2025.104791","url":null,"abstract":"<div><div>During cellular stress, which results in DNA damage, protein, glucose, and lipid metabolism disorders, and redox homeostasis imbalance, various cellular stress responses are triggered, such as DNA damage response, endoplasmic reticulum stress, integrated stress response, and oxidative stress. These cellular stress responses play an important role in the disease process and have a dual role. Activating transcription factor3 belongs to the ATF/CREB family and is activated by stress. It is a transcription factor that plays an important role in gene regulation. It mainly participates in the regulation of disease progression by regulating metabolic homeostasis. Its expression is related to the prognosis of various tumors. ATF3, which is elevated in tumor cells by stress stimulation, not only participates in the repair of internal environment homeostasis mediated by cellular stress response, but also plays a key role in programmed cell death mediated by cellular stress response. Cellular stress response can affect the occurrence of ferroptosis through multiple pathways, with ATF3 being a key protein. This review first introduces the mechanism of ATF3 expression regulation, then summarizes the dual role of ATF3 in DNA damage response, endoplasmic reticulum stress, integrated stress response, and oxidative stress. Finally, it emphasizes the mechanism of ATF3 affecting ferroptosis through DNA damage response, and ER and oxidative stress. This study comprehensively reviews the role of ATF3 in tumors from multiple perspectives, providing new directions for tumor treatment.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"213 ","pages":"Article 104791"},"PeriodicalIF":5.5,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236146","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}

{"title":"Targeting c-MYC has a key role in hepatocellular carcinoma therapy","authors":"Peng Dai ,&nbsp;Liping Wang","doi":"10.1016/j.critrevonc.2025.104786","DOIUrl":"10.1016/j.critrevonc.2025.104786","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is a top cause of cancer-associated mortality worldwide, with limited effective treatment options. The oncogenic transcription factor c-MYC plays a pivotal role in HCC pathogenesis by regulating key cellular processes, including proliferation, metabolism, and apoptosis. Impaired c-MYC regulation strongly correlates with aberrant activation of multiple signaling pathways, such as PI3K/Akt/mTOR, Wnt/β-catenin, and MAPK/ERK, which collectively drive tumor progression. Furthermore, c-MYC facilitates metabolic reprogramming, enhancing glycolysis and glutamine metabolism to support rapid tumor growth. Recent advances highlight the critical interplay between c-MYC and epigenetic modulators, ubiquitination processes, and non-coding RNAs, which further sustain its oncogenic activity. Targeting c-MYC through direct inhibition, pathway-specific interventions, and combination therapies stands as a compelling option for HCC treatment. This review offers an in-depth overview of the molecular mechanisms governing c-MYC-driven hepatocarcinogenesis and explores emerging therapeutic approaches aimed at disrupting this oncogenic network. A deeper understanding of c-MYC’s role in HCC will pave the way for novel treatment strategies with potential clinical applications.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"213 ","pages":"Article 104786"},"PeriodicalIF":5.5,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236145","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}

{"title":"Tissue spacers in brachytherapy: A systematic review and meta-analysis","authors":"Mohammad Hossein Sadeghi ,&nbsp;Zahra Siavashpour ,&nbsp;Sedigheh Sina","doi":"10.1016/j.critrevonc.2025.104790","DOIUrl":"10.1016/j.critrevonc.2025.104790","url":null,"abstract":"<div><div>To systematically evaluate the impact of tissue spacers on radiation dose reduction to organs at risk (OARs), treatment-related toxicity, and overall clinical outcomes in brachytherapy, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A thorough search of PubMed, Scopus, IEEE Xplore, Embase, and Web of Science was conducted (1990–2024). Eligible studies included randomized trials, prospective or retrospective cohorts, and dosimetric analyses examining spacer use in brachytherapy. Data were extracted on patient demographics, spacer characteristics, dosimetric outcomes, and toxicity. Meta-analyses were performed where at least three studies reported comparable quantitative data, using random-effects models to pool effect sizes. Forty-five studies met inclusion criteria; 24 contributed to quantitative pooling. In prostate brachytherapy, hydrogel or balloon spacers consistently lowered rectal dose metrics by approximately 15–50 % and significantly reduced Grade ≥ 2 gastrointestinal toxicity (risk ratio ∼0.42). For head and neck brachytherapy, custom acrylic or silicone spacers decreased jaw dose and markedly lowered osteoradionecrosis rates. In gynecologic cancers, spacer balloons or injectable gels yielded 10–20 % reductions in bladder or rectal doses. Across all sites, spacers generally did not compromise tumor coverage and were associated with fewer late complications and improved patient quality of life. Spacers substantially improve the therapeutic ratio in brachytherapy by reducing OAR doses and lowering clinically significant toxicities. While the evidence base supports integrating spacers into standard practice, further randomized, multicenter trials are warranted to refine optimal spacer designs, placement techniques, and cost-effectiveness analyses.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"213 ","pages":"Article 104790"},"PeriodicalIF":5.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205653","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}

{"title":"Adverse effect of trastuzumab deruxtecan in solid tumours: A systematic review and meta-analysis","authors":"Neha Pathak ,&nbsp;Massimo Di Iorio ,&nbsp;Diego Malon Gimenez ,&nbsp;Yael Berner-Wygoda ,&nbsp;Jacqueline Savill ,&nbsp;Amal Aljuhani ,&nbsp;Abhenil Mittal ,&nbsp;Vikaash Kumar ,&nbsp;Eitan Amir","doi":"10.1016/j.critrevonc.2025.104787","DOIUrl":"10.1016/j.critrevonc.2025.104787","url":null,"abstract":"<div><h3>Introduction</h3><div>Trastuzumab deruxtecan (T-DXd) is approved for use in numerous solid tumours. Here we summarize its safety and tolerability profile.</div></div><div><h3>Methods</h3><div>Studies were identified from MEDLINE, EMBASE and recent conference proceedings. Analysis comprised clinical trials (phases 1 [dose-expansion], 2 or 3) reporting safety and tolerability of T-DXd. Data were pooled as the mean weighted by individual study sample size from single arm studies. Randomized studies were analyzed separately to compare T-DXd to chemotherapy and to trastuzumab emtansine. Meta regression comprised linear regression weighted by sample size was performed.</div></div><div><h3>Results</h3><div>A total of 35 studies with 48 distinct cohorts were included in the analysis. All grade adverse effects (AEs) and grade ≥ 3 AEs occurred in 97.2 % and 54.9 % of patients respectively. Most common all grade AEs included: nausea (66.2 %), fatigue (41.8 %) and anemia (33.8 %). Common grade ≥ 3 AEs included anemia (12.9 %), thrombocytopenia (6.7 %) and fatigue (5.3 %). Pooled incidence rate of interstitial lung disease (ILD) and grade≥ 3 ILD were 13.2 % and 2.3 % respectively, and 2 % had febrile neutropenia. Cardiotoxicity was rare. Treatment- and ILD- related deaths were reported in 5 % and ILD 1.4 %, respectively. Compared to chemotherapy, T-DXd had higher odds of AEs and treatment discontinuation. Higher dose, non-Caucasian ethnicity and cancer sites other than breast were associated with grade ≥ 3 AE, grade ≥ 3 ILD, AE- and ILD- related deaths and serious AEs.</div></div><div><h3>Conclusions</h3><div>T-DXd has a safety and tolerability profile less favorable than classical chemotherapy. Dose, ethnicity and cancer site are associated with differential safety and tolerability.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"213 ","pages":"Article 104787"},"PeriodicalIF":5.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205654","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}

{"title":"Anaemia in cancer patients: Advances and challenges in the era of precision oncology","authors":"Federica Miglietta ,&nbsp;Mario Pirozzi ,&nbsp;Michele Bottosso ,&nbsp;Carla Pisani ,&nbsp;Pierfrancesco Franco ,&nbsp;Valentina Guarnieri ,&nbsp;Alessandra Gennari","doi":"10.1016/j.critrevonc.2025.104788","DOIUrl":"10.1016/j.critrevonc.2025.104788","url":null,"abstract":"<div><div>Anaemia in cancer patients is an independent prognostic factor associated with reduced survival and increased morbidity. Aetiology of anaemia in cancer patients is multifactorial, involving complex interactions between the cancer itself, treatment modalities, and patient-specific factors. Although anaemia is traditionally associated with cytotoxic chemotherapy, newer drugs can still cause haemoglobin reduction by blood loss, erythrocytes impaired production and increased destruction or reduced survival. A view on the different impact of newer drugs will be presented in our review. Data on the impact of anaemia on quality of life, according to several scales specifically designed for cancer-associated anaemia, will also be reported. Finally, we report on recent guidelines and advances in anaemia management: oral and intravenous iron supplementation, red blood cells transfusions and erythropoiesis-stimulating agents.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"213 ","pages":"Article 104788"},"PeriodicalIF":5.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144227987","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}

{"title":"Stereotactic body radiotherapy as an alternative to brachytherapy in cervical cancer (SCORE): A systematic review and meta-analysis","authors":"Jessé Lopes da Silva ,&nbsp;Ana Verena Silvany Sampaio de Miranda ,&nbsp;Gustavo Viani Arruda ,&nbsp;Diocésio Alves Pinto de Andrade ,&nbsp;Larissa Müller Gomes ,&nbsp;Marcela Bonalumi dos Santos ,&nbsp;Kleyton Santos de Medeiros ,&nbsp;Andréia Cristina de Melo","doi":"10.1016/j.critrevonc.2025.104789","DOIUrl":"10.1016/j.critrevonc.2025.104789","url":null,"abstract":"<div><h3>Objective</h3><div>This study evaluates the efficacy and safety of Stereotactic Body Radiotherapy (SBRT) as an alternative to brachytherapy (BCT) for patients with locally advanced cervical cancer (CC) who face barriers such as resource constraints, anatomical challenges, or comorbidities precluding standard treatment.</div></div><div><h3>Methods</h3><div>A systematic review and meta-analysis, registered with PROSPERO and adhered to PRISMA standards, was conducted to evaluate SBRT in place of BCT for CC treatment. Eligible studies were systematically sourced from PubMed, Embase, and Cochrane databases. A random-effects model was applied to address study heterogeneity. The analysis focused on outcomes including local control (LC), late gastrointestinal (GI) and genitourinary (GU) toxicity, and overall survival (OS) rates with meta-regression exploring correlations between treatment variables and outcomes.</div></div><div><h3>Results</h3><div>The review analyzed thirteen studies from 2012 to 2024 across diverse regions, with participant ages ranging from 52 to 80 years and sample sizes from 6 to 55 patients. The combined LC rate was 94 % (95 % CI: 91–97 %), and the OS rate was 56 % (95 % CI: 48–63 %), showing no heterogeneity. Late grade ≥ 3 GI and GU toxicity were both 2 %. Meta-regression analysis found no significant associations between treatment parameters and the analyzed outcomes.</div></div><div><h3>Conclusion</h3><div>SBRT is a viable boost therapy for CC patients unable to undergo BCT. It demonstrates strong LC and low levels of severe late toxicity. Further prospective randomized trials are necessary to refine SBRT protocols and confirm long-term outcomes.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"213 ","pages":"Article 104789"},"PeriodicalIF":5.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144213284","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}

{"title":"Impact of the tumor microenvironment on progression and treatment response in lymphoma and chronic lymphocytic leukemia: A systematic review of the literature","authors":"Sebastian Villamizar Castellanos ,&nbsp;Maria Paula Rodriguez Castellanos ,&nbsp;Maria Camila Gil Avendaño ,&nbsp;Mary Cielo Arias Asprilla ,&nbsp;Miguel Santiago Garcia Leal ,&nbsp;Gloria Tirado","doi":"10.1016/j.critrevonc.2025.104782","DOIUrl":"10.1016/j.critrevonc.2025.104782","url":null,"abstract":"<div><h3>Introduction</h3><div>The tumor microenvironment (TME) plays a critical role in the progression of lymphomas and chronic lymphocytic leukemia (CLL). Comprising immune cells, cytokines, growth factors, and the extracellular matrix, it modulates therapeutic resistance and tumor aggressiveness. Key elements such as Tregs and TAMs induce immunosuppression, while cytokines like IL-6 promote malignant cell proliferation and survival.</div></div><div><h3>Objective</h3><div>To synthesize evidence regarding the influence of the TME on the progression and treatment response in lymphoma and CLL, identifying knowledge gaps and potential therapeutic targets.</div></div><div><h3>Methods</h3><div>A systematic review was conducted following PRISMA guidelines, including 17 studies published between 2000–2024 on the TME in lymphoma and CLL. Primary outcomes included overall survival (OS), progression-free survival (PFS), and treatment response rates. Searches included databases such as PubMed, Scopus, and Cochrane.</div></div><div><h3>Results</h3><div>Elevated IL-6 levels were associated with worse OS in aggressive lymphomas (mean OS 43.3 months in IL-6 positive patients vs. 96.0 months in negative, <em>p</em> &lt; 0.001). A high proportion of Tregs in the TME correlated with shorter PFS (53 % at 5 years vs. 72 %, <em>p</em> = 0.013). In CLL, treatment with BTK inhibitors favorably modified the Th2/Th1 ratio (<em>p</em> &lt; 0.002), improving clinical responses.</div></div><div><h3>Discussion</h3><div>The findings confirm the relevance of the TME as a determinant of clinical and prognostic heterogeneity. IL-6 and Tregs emerge as key biomarkers and therapeutic targets. Strategies aimed at reversing immunosuppression could optimize clinical outcomes; however, methodological limitations persist, such as heterogeneity in TME characterization methods.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"213 ","pages":"Article 104782"},"PeriodicalIF":5.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217862","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}