Oncoimmunology最新文献

{"title":"Enhancing T-cell recruitment in renal cell carcinoma with cytokine-armed adenoviruses.","authors":"Michaela Feodoroff, Firas Hamdan, Gabriella Antignani, Sara Feola, Manlio Fusciello, Salvatore Russo, Jacopo Chiaro, Katja Välimäki, Teijo Pellinen, Rui M Branca, Janne Lehtiö, Federica D Alessio, Paolo Bottega, Virpi Stigzelius, Janita Sandberg, Jonna Clancy, Jukka Partanen, Minna Malmstedt, Antti Rannikko, Vilja Pietiäinen, Mikaela Grönholm, Vincenzo Cerullo","doi":"10.1080/2162402X.2024.2407532","DOIUrl":"10.1080/2162402X.2024.2407532","url":null,"abstract":"<p><p>Immunotherapy has emerged as a promising approach for cancer treatment, with oncolytic adenoviruses showing power as immunotherapeutic agents. In this study, we investigated the immunotherapeutic potential of an adenovirus construct expressing CXCL9, CXCL10, or IL-15 in clear cell renal cell carcinoma (ccRCC) tumor models. Our results demonstrated robust cytokine secretion upon viral treatment, suggesting effective transgene expression. Subsequent analysis using resistance-based transwell migration and microfluidic chip assays demonstrated increased T-cell migration in response to chemokine secretion by infected cells in both 2D and 3D cell models. Flow cytometry analysis revealed CXCR3 receptor expression across T-cell subsets, with the highest percentage found on CD8+ T-cells, underscoring their key role in immune cell migration. Alongside T-cells, we also detected NK-cells in the tumors of immunocompromised mice treated with cytokine-encoding adenoviruses. Furthermore, we identified potential immunogenic antigens that may enhance the efficacy and specificity of our armed oncolytic adenoviruses in ccRCC. Overall, our findings using ccRCC cell line, <i>in vivo</i> humanized mice, physiologically relevant PDCs in 2D and patient-derived organoids (PDOs) in 3D suggest that chemokine-armed adenoviruses hold promise for enhancing T-cell migration and improving immunotherapy outcomes in ccRCC. Our study contributes to the development of more effective ccRCC treatment strategies by elucidating immune cell infiltration and activation mechanisms within the tumor microenvironment (TME) and highlights the usefulness of PDOs for predicting clinical relevance and validating novel immunotherapeutic approaches. Overall, our research offers insights into the rational design and optimization of viral-based immunotherapies for ccRCC.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2407532"},"PeriodicalIF":6.5,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11441019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142356459","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}

{"title":"Immune priming and induction of tertiary lymphoid structures in a cord-blood humanized mouse model of gastrointestinal stromal tumor.","authors":"Bo He, Larissa Dymond, Kira H Wood, Edward R Bastow, Jiulia Satiaputra, Ji Li, Anna Johansson-Percival, Juliana Hamzah, M Priyanthi Kumarasinghe, Mohammed Ballal, Jonathan Foo, Mikael Johansson, Hooi C Ee, Scott W White, Louise Winteringham, Ruth Ganss","doi":"10.1080/2162402X.2024.2406576","DOIUrl":"10.1080/2162402X.2024.2406576","url":null,"abstract":"<p><p>Gastrointestinal stromal tumors (GISTs) harbor diverse immune cell populations but so far immunotherapy in patients has been disappointing. Here, we established cord blood humanized mouse models of localized and disseminated GIST to explore the remodeling of the tumor environment for improved immunotherapy. Specifically, we assessed the ability of a cancer vascular targeting peptide (VTP) to bind to mouse and patient GIST angiogenic blood vessels and deliver the TNF superfamily member LIGHT (TNFS14) into tumors. LIGHT-VTP treatment of GIST in humanized mice improved vascular function and tumor oxygenation, which correlated with an overall increase in intratumoral human effector T cells. Concomitant with LIGHT-mediated vascular remodeling, we observed intratumoral high endothelial venules (HEVs) and tertiary lymphoid structures (TLS), which resemble spontaneous TLS found in GIST patients. Thus, by overcoming the limitations of immunodeficient xenograft models, we demonstrate the therapeutic feasibility of vascular targeting and immune priming in human GIST. Since TLS positively correlate with patient prognosis and improved response to immune checkpoint inhibition, vascular LIGHT targeting in GIST is a highly translatable approach to improve immunotherapeutic outcomes.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2406576"},"PeriodicalIF":6.5,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308843","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}

{"title":"CD4⁺ tumor-infiltrating lymphocytes secreting T cell-engagers induce regression of autologous patient-derived non-small cell lung cancer xenografts.","authors":"Anaïs Jiménez-Reinoso, Magdalena Molero-Abraham, Cristina Cirauqui, Belén Blanco, Eva M Garrido-Martin, Daniel Nehme-Álvarez, Carmen Domínguez-Alonso, Ángel Ramírez-Fernández, Laura Díez-Alonso, Ángel Nuñez-Buiza, África González-Murillo, Raquel Tobes, Eduardo Pareja, Manuel Ramírez-Orellana, José Luis Rodriguez-Peralto, Irene Ferrer, Jon Zugazagoitia, Luis Paz-Ares, Luis Álvarez-Vallina","doi":"10.1080/2162402X.2024.2392897","DOIUrl":"10.1080/2162402X.2024.2392897","url":null,"abstract":"<p><p>Adoptive transfer of tumor-infiltrating lymphocytes (TIL) has shown remarkable results in melanoma, but only modest clinical benefits in other cancers, even after TIL have been genetically modified to improve their tumor homing, cytotoxic potential or overcome cell exhaustion. The required <i>ex vivo</i> TIL expansion process may induce changes in the T cell clonal composition, which could likely compromise the tumor reactivity of TIL preparations and ultimately the success of TIL therapy. A promising approach based on the production of bispecific T cell-engagers (TCE) by engineered T cells (STAb-T therapy) improves the efficacy of current T cell redirection strategies against tumor-associated antigens in hematological tumors. We studied the TCRβ repertoire in non-small cell lung cancer (NSCLC) tumors and in <i>ex vivo</i> expanded TIL from two unrelated patients. We generated TIL secreting anti-epidermal growth factor receptor (EGFR) × anti-CD3 TCE (TIL^STAb) and tested their antitumor efficacy <i>in vitro</i> and <i>in vivo</i> using a NSCLC patient-derived xenograft (PDX) model in which tumor fragments and TIL from the same patient were transplanted into <i>hIL-2</i> NOG mice. We confirmed that the standard TIL expansion protocol promotes the loss of tumor-dominant T cell clones and the overgrowth of virus-reactive TCR clonotypes that were marginally detectable in primary tumors. We demonstrated the antitumor activity of TIL^STAb both <i>in vitro</i> and <i>in vivo</i> when administered intratumorally and systemically in an autologous immune-humanized PDX EGFR⁺ NSCLC mouse model, where tumor regression was mediated by TCE-redirected CD4⁺ TIL bearing non-tumor dominant clonotypes.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2392897"},"PeriodicalIF":6.5,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11352715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142113732","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}

{"title":"Metabolic regulation of the mitochondrial immune checkpoint.","authors":"David C Montrose, Suchandrima Saha, Lorenzo Galluzzi","doi":"10.1080/2162402X.2024.2394247","DOIUrl":"10.1080/2162402X.2024.2394247","url":null,"abstract":"<p><p>Disrupting mitochondrial function in malignant cells is a promising strategy to enhance anticancer immunity. We have recently demonstrated that depriving colorectal cancer cells of serine results in mitochondrial dysfunction coupled with the cytosolic accumulation of mitochondrial DNA and consequent activation of CGAS- and STING-dependent tumor-targeting immune responses.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2394247"},"PeriodicalIF":6.5,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11352702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142113733","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}

{"title":"Overexpression of CCL-20 and CXCL-8 genes enhances tumor escape and resistance to cemiplimab, a programmed cell death protein-1 (PD-1) inhibitor, in patients with locally advanced and metastatic cutaneous squamous cell carcinoma.","authors":"Vincenzo De Falco, Stefania Napolitano, Renato Franco, Federica Zito Marino, Luigi Formisano, Daniela Esposito, Gabriella Suarato, Rossella Napolitano, Alfonso Esposito, Francesco Caraglia, Maria Cristina Giugliano, Eleonora Cioli, Vincenzo Famiglietti, Roberto Bianco, Giuseppe Argenziano, Andrea Ronchi, Davide Ciardiello, Valerio Nardone, Emma D'Ippolito, Sara Del Tufo, Fortunato Ciardiello, Teresa Troiani","doi":"10.1080/2162402X.2024.2388315","DOIUrl":"10.1080/2162402X.2024.2388315","url":null,"abstract":"<p><p>Cemiplimab has demonstrated relevant clinical activity in cutaneous squamous cell carcinoma (cSCC) but mechanisms of primary and acquired resistance to immunotherapy are still unknown. We collected clinical data from locally advanced and/or metastatic cSSC patients treated with cemiplimab in two Italian University centers. In addition, gene expression analysis by using Nanostring Technologies platform to evaluate 770 cancer- and immune-related genes on 20 tumor tissue samples (9 responders and 11 non-responders to cemiplimab) was performed. We enrolled 81 patients with a median age of 82 years. After 16.4 months of median follow-up, 12- and 24-months PFS were 53% and 42%, respectively; while 12- and 24-months OS were 71% and 61%, respectively. Treatment was well tolerated. Overall response rate (ORR) was 58%, with a disease control rate (DCR) of 77.8%. The difference between genes expressed in responder versus non-responder patient samples was substantial, particularly for genes involved in immune system regulation. Cemiplimab-resistant tumors were associated with over-expression of CCL-20 and CXCL-8. Cemiplimab confirmed efficacy and safety data in real-life cSCC patients. Overexpression of CCL-20 and CXCL-8 could represent biomarkers of lack of response to immunotherapy.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2388315"},"PeriodicalIF":6.5,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11352706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142113734","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}

{"title":"Local therapy with combination TLR agonists stimulates systemic anti-tumor immunity and sensitizes tumors to immune checkpoint blockade.","authors":"Francois Xavier Rwandamuriye, Tao Wang, Hanfu Zhang, Omar Elaskalani, Jorren Kuster, Xueting Ye, Breana Vitali, Juliët Schreurs, M Lizeth Orozco Morales, Marck Norret, Cameron W Evans, Rachael M Zemek, K Swaminathan Iyer, W Joost Lesterhuis, Ben Wylie","doi":"10.1080/2162402X.2024.2395067","DOIUrl":"10.1080/2162402X.2024.2395067","url":null,"abstract":"<p><p>Toll-like receptor (TLR) agonists are being developed as anti-cancer therapeutics due to their potent immunostimulatory properties. However, clinical trials testing TLR agonists as monotherapy have often failed to demonstrate significant improvement over standard of care. We hypothesized that the anti-cancer efficacy of TLR agonist immunotherapy could be improved by combinatorial approaches. To prevent increased toxicity, often seen with systemic combination therapies, we developed a hydrogel to deliver TLR agonist combinations at low doses, locally, during cancer debulking surgery. Using tumor models of WEHI 164 and bilateral M3-9-M sarcoma and CT26 colon carcinoma, we assessed the efficacy of pairwise combinations of poly(I:C), R848, and CpG in controlling local and distant tumor growth. We show that combination of the TLR3 agonist poly(I:C) and TLR7/8 agonist R848 drives anti-tumor immunity against local and distant tumors. In addition, combination of local poly(I:C) and R848 sensitized tumors to systemic immune checkpoint blockade, improving tumor control. Mechanistically, we demonstrate that local therapy with poly(I:C) and R848 recruits inflammatory monocytes to the tumor draining lymph nodes early in the anti-tumor response. Finally, we provide proof of concept for intraoperative delivery of poly(I:C) and R848 together via a surgically applicable biodegradable hydrogel.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2395067"},"PeriodicalIF":6.5,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11346538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074255","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}

{"title":"Tertiary lymphoid structure-related immune infiltrates in NSCLC tumor lesions correlate with low tumor-reactivity of TIL products.","authors":"Suzanne M Castenmiller, Nandhini Kanagasabesan, Aurélie Guislain, Benoît P Nicolet, Marleen M van Loenen, Kim Monkhorst, Alexander A F A Veenhof, Egbert F Smit, Koen J Hartemink, John B A G Haanen, Rosa de Groot, Monika C Wolkers","doi":"10.1080/2162402X.2024.2392898","DOIUrl":"10.1080/2162402X.2024.2392898","url":null,"abstract":"<p><p>Adoptive transfer of tumor infiltrating lymphocytes (TIL therapy) has proven highly effective for treating solid cancers, including non-small cell lung cancer (NSCLC). However, not all patients benefit from this therapy for yet unknown reasons. Defining markers that correlate with high tumor-reactivity of the autologous TIL products is thus key for achieving better tailored immunotherapies. We questioned whether the composition of immune cell infiltrates correlated with the tumor-reactivity of expanded TIL products. Unbiased flow cytometry analysis of immune cell infiltrates of 26 early-stage and 20 late-stage NSCLC tumor lesions was used for correlations with the T cell differentiation and activation status, and with the expansion rate and anti-tumor response of generated TIL products. The composition of tumor immune infiltrates was highly variable between patients. Spearman's Rank Correlation revealed that high B cell infiltration negatively correlated with the tumor-reactivity of the patient's expanded TIL products, as defined by cytokine production upon exposure to autologous tumor digest. In-depth analysis revealed that tumor lesions with high B cell infiltrates contained tertiary lymphoid structure (TLS)-related immune infiltrates, including BCL6⁺ antibody-secreting B cells, IgD⁺BCL6⁺ B cells and CXCR5⁺BLC6⁺ CD4⁺ T cells, and higher percentages of naïve CD8⁺ T cells. In conclusion, the composition of immune cell infiltrates in NSCLC tumors associates with the functionality of the expanded TIL product. Our findings may thus help improve patient selection for TIL therapy.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2392898"},"PeriodicalIF":6.5,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11346574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074256","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}

{"title":"Secreted factors from M1 macrophages drive prostate cancer stem cell plasticity by upregulating NANOG, <i>SOX2</i>, and <i>CD44</i> through NFκB-signaling.","authors":"Kirsi Kainulainen, Einari A Niskanen, Johanna Kinnunen, Kaisa Mäki-Mantila, Kiia Hartikainen, Ville Paakinaho, Marjo Malinen, Kirsi Ketola, Sanna Pasonen-Seppänen","doi":"10.1080/2162402X.2024.2393442","DOIUrl":"10.1080/2162402X.2024.2393442","url":null,"abstract":"<p><p>The inflammatory tumor microenvironment (TME) is a key driver for tumor-promoting processes. Tumor-associated macrophages are one of the main immune cell types in the TME and their increased density is related to poor prognosis in prostate cancer. Here, we investigated the influence of pro-inflammatory (M1) and immunosuppressive (M2) macrophages on prostate cancer lineage plasticity. Our findings reveal that M1 macrophage secreted factors upregulate genes related to stemness while downregulating genes associated with androgen response in prostate cancer cells. The expression of cancer stem cell (CSC) plasticity markers NANOG, KLF4, <i>SOX2, OCT4</i>, and CD44 was stimulated by the secreted factors from M1 macrophages. Moreover, AR and its target gene <i>PSA</i> were observed to be suppressed in LNCaP cells treated with secreted factors from M1 macrophages. Inhibition of NFκB signaling using the IKK16 inhibitor resulted in downregulation of NANOG, <i>SOX2</i>, and <i>CD44</i> and CSC plasticity. Our study highlights that the secreted factors from M1 macrophages drive prostate cancer cell plasticity by upregulating the expression of CSC plasticity markers through NFκB signaling pathway.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2393442"},"PeriodicalIF":6.5,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034397","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}

{"title":"<i>FCGR3A</i> F158V alleles frequency differs in multiple myeloma patients from healthy population.","authors":"Michaël Constantinides, Nicolas Robert, Caroline Multrier, Loïs Coënon, Mauricio Campos-Mora, Carine Jacquard, Fei Gao, Sara Zemiti, Jessy Presumey, Guillaume Cartron, Jérome Moreaux, Martin Villalba","doi":"10.1080/2162402X.2024.2388306","DOIUrl":"10.1080/2162402X.2024.2388306","url":null,"abstract":"<p><p><i>FCGR3A</i> presents a single nucleotide polymorphism at location 158 (V/F), which affects its binding to the fragment crystallizable (Fc) of antibodies (Abs). FcγRIIIa-158 V allotype has the highest affinity and is associated with a better clinical response to IgG1 monoclonal Abs (mAb) treatment. We compared the allele frequency of <i>FCGR3A-</i>F158V polymorphism in cohorts of patients with B-cell lymphoproliferative disorders, including multiple myeloma (MM), monoclonal gammopathy of undetermined significance (MGUS), non-Hodgkin lymphoma (NHL), and B-cell chronic leukemia (B-CLL). <i>FCGR3A</i>-158F homozygous were enriched and tended to be in MM and MGUS patients, respectively; but neither in B-CLL nor in NHL patients. We identified a significantly lower concentration of CD8 T-cells and resting memory CD4 T-cells in MM patients bone marrow with the F/F genotype, associated with an increase in the macrophage percentage. In contrast, natural killer cells increased in V/V homozygous patients. This suggests a deregulation of the immune microenvironment in <i>FCGR3A</i>-F/F homozygous patients. However, we did not observe difference in response following treatment combining chemotherapy associated or not with daratumumab, an IgG1 mAb direct against CD38. Our findings suggest that <i>FCGR3A</i> F158V polymorphism can regulate the immune environment and affect the development of tumor plasma cells.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2388306"},"PeriodicalIF":6.5,"publicationDate":"2024-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037402","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}

{"title":"Correction.","authors":"","doi":"10.1080/2162402X.2024.2351662","DOIUrl":"https://doi.org/10.1080/2162402X.2024.2351662","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1080/2162402X.2015.1055993.].</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2351662"},"PeriodicalIF":6.5,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11321395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141977638","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}