Cancer research communications最新文献

{"title":"Cervical cancer patients with and without HIV infection have unique T cell activation profiles despite similar survival outcomes after chemoradiation.","authors":"Emily C MacDuffie, Luis Cocka, Xiang Lin, Memory Bvochora-Nsingo, Sebathu Chiyapo, Dawn Balang, Bokang Maswabi, Kebatshabile Ngoni, Doreen Ramogola-Masire, Nicola M Zetola, Zhi Wei, Hao Shen, Sheynaz Bassa, Surbhi Grover, Erle S Robertson","doi":"10.1158/2767-9764.CRC-24-0364","DOIUrl":"https://doi.org/10.1158/2767-9764.CRC-24-0364","url":null,"abstract":"<p><p>The global burden of cervical cancer is highest in low- and middle-income countries (LMICs). Women living with HIV infection are particularly impacted by cervical cancer despite availability and adherence to antiretroviral therapy (ART). Immune profile correlates of survival and treatment response have not been widely explored in patients with and without HIV infection. This study recruited women with cervical cancer undergoing definitive chemoradiation (CRT) in Botswana. Clinical characteristics and blood samples were collected. Flow cytometry was performed on samples prior to initiation (Initial), at completion (EOT), and three months after (M3) CRT. Logistic regression analysis identified immune markers that differed by HIV status and correlated with overall survival (OS). The study enrolled 131 consecutive women (HIV+ N=89, HIV- N=42). From Initial to M3, a significant decrease in CD4 frequency (72% to 60.55%, p<0.001) and increase in CD8 frequency (20.9% to 31.5%, p<0.001) was seen in women without HIV whereas no significant changes in CD4 frequency (52.5% to 50.9%) or CD8 frequency (39.9% to 41.4%) were observed in those with HIV. Peripheral T cells underwent similar activation across the cohort regardless of HIV status. Improved OS was associated with reduced frequency of IL-2 expressing CD4 T cell subsets. In women living with HIV, enhanced OS was associated with the presence of proinflammatory CD8 T cells. CRT induces peripheral T cell activation and distinct cytokine profiles that differ by HIV status. Despite similar OS, HIV infection may differentially impact immune response to CRT in women with well-managed disease.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143659446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Blood-based Assay for Detection of Patients with Advanced Adenomas.","authors":"Kamel Lahouel, Christopher Douville, Brenda Diergaarde, Joshua D Cohen, Haley Grant, Albert Kuo, Saad K Ansari, Yuxuan Wang, Anne Marie O'Broin-Lennon, Maria Popoli, Janine Ptak, Natalie Silliman, Lisa Dobbyn, Nadine Nehme, Jeanne Tie, Peter Gibbs, Nickolas Papadopoulos, Kenneth W Kinzler, Bert Vogelstein, Robert E Schoen, Cristian Tomasetti","doi":"10.1158/2767-9764.CRC-24-0398","DOIUrl":"https://doi.org/10.1158/2767-9764.CRC-24-0398","url":null,"abstract":"<p><p>Screening for colorectal cancer (CRC) with blood-based testing should detect advanced adenomas (AAs), facilitating more effective cancer prevention. We evaluated four different methods to detect AAs in plasma: (a) a machine-learning algorithm, SignaL (Signatures of fragment Length), based on cell-free DNA (cfDNA) fragmentation; (b) a \"Protein-17\" assay measuring 17 cancer-associated proteins; (c) a Global Aneuploidy Score (GAS); and (d) cfDNA mutation analysis querying 15 genes commonly mutated in CRC. Existing data from study populations with and without cancer were utilized to determine 99.5% specificity thresholds. We studied 40 AA cases and 32 colonoscopy-negative controls. SignaL detected 9/40 AAs (22.5%, 95%CI: 12.3-37.5%) at 100% specificity (95%CI: 89.3-100%). Protein-17 detected 5/40 AAs (12.5%, 95%CI: 5.5-26.1%) including three cases not identified by SignaL, at 100% specificity (95%CI: 89.3 to 100%). GAS detected 11/40 AAs (27.5%, 95%CI: 16.1-42.8%), but resulted in 2/32 positive controls (93.8% specificity, 95%CI: 79.9-98.3%). Combining SignaL, the Protein-17 assay, and GAS at the 99.5% specificity thresholds resulted in detection of 16/40 AAs (40%, 95% CI:26.3-55.4%) at 93.8% specificity (95% CI: 79.9% to 98.3%). Of 32/40 evaluable AA plasma samples, only one was cfDNA mutation positive at 0.01 level of significance. A blood-based assay based on the analysis of repeated sequence elements plus proteins appears to be able to detect a considerable fraction of patients with AA at relatively high specificity. Large, prospective studies are required to determine whether this approach can add to the options currently available for screening patients for pre-malignant lesions of the colon.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143659517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and Efficacy of Copanlisib in Combination with Nivolumab: A Phase Ib Study in Patients with Advanced Solid Tumors.","authors":"Benedito A Carneiro, Robert M Jotte, Nashat Y Gabrail, Kristopher Wentzel, Funan Huang, Shalini Chaturvedi, Anke Weispfenning, Florian Hiemeyer, Peter N Morcos, Lidia Mongay Soler, Barrett H Childs, Aaron R Hansen","doi":"10.1158/2767-9764.CRC-24-0407","DOIUrl":"10.1158/2767-9764.CRC-24-0407","url":null,"abstract":"<p><strong>Purpose: </strong>Copanlisib in combination with immune checkpoint inhibitors demonstrated synergy and favorable antitumor immune responses in preclinical models. This study evaluated copanlisib plus nivolumab in adults with advanced solid tumors.</p><p><strong>Patients and methods: </strong>In this phase Ib, nonrandomized, open-label, dose-escalation study, patients received intravenous nivolumab 240 mg (day 15 of cycle 1 and days 1 and 15 of subsequent cycles) plus intravenous copanlisib (45 or 60 mg on days 1, 8, and 15 of each cycle) in 28-day cycles. The primary objective was to determine the MTD and/or recommended phase II dose of copanlisib plus nivolumab. Secondary objectives were safety, tolerability, and efficacy. Exploratory objectives included evaluation of potentially predictive biomarkers.</p><p><strong>Results: </strong>Overall, 16 patients were treated [copanlisib: 45 mg (n = 5); 60 mg (n = 11)]. The most common cancer types at baseline were bladder (25.0%) and oropharyngeal (18.8%) cancers. No dose-limiting toxicities were observed; copanlisib 60 mg was deemed the recommended phase II dose in combination with nivolumab 240 mg. Grade 3 and 4 treatment-emergent adverse events were reported in 56.3% and 12.5% of patients, respectively; one grade 5 event was reported (unrelated to treatment). Overall, 18.8% of patients achieved a partial response. Evaluations of potential biomarkers did not correlate with response, but copanlisib-modulated biomarker changes were observed before nivolumab administration and were consistent and dose-dependent.</p><p><strong>Conclusions: </strong>No new safety concerns were identified with this combination, and preliminary efficacy indicated an antitumor effect. Data supported an immunomodulatory effect of copanlisib, suggesting that this combination may enhance the efficacy of immune checkpoint inhibitors.</p><p><strong>Significance: </strong>The combination of copanlisib and nivolumab was well tolerated and showed antitumor effects in patients with advanced solid tumors. The number of circulating myeloid-derived suppressive cells decreased 24 to 48 hours after treatment with copanlisib. Further investigation of copanlisib and nivolumab is warranted as a novel strategy to enhance the efficacy of checkpoint inhibitors.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"444-457"},"PeriodicalIF":2.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143384291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Causal Plasma Proteins in Hepatocellular Carcinoma via Two-Sample Mendelian Randomization and Integrative Transcriptomic‒Proteomic Analysis.","authors":"Weihao Tang, Xiaoke Ma","doi":"10.1158/2767-9764.CRC-24-0553","DOIUrl":"10.1158/2767-9764.CRC-24-0553","url":null,"abstract":"<p><strong>Significance: </strong>In this study, we identified several causal proteins in HCC using UK Biobank Pharma Proteomics Project proteomic data via two-sample MR. We performed colocalization and sensitivity analyses, utilized single-cell RNA sequencing data for validation, and discovered potential drugs through molecular docking.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"433-443"},"PeriodicalIF":2.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11897958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a Microvessel Density Gene Signature and Its Application in Precision Medicine.","authors":"Megumi Kuronishi, Yoichi Ozawa, Takayuki Kimura, Shuyu Dan Li, Yu Kato","doi":"10.1158/2767-9764.CRC-24-0403","DOIUrl":"10.1158/2767-9764.CRC-24-0403","url":null,"abstract":"<p><strong>Significance: </strong>A novel gene signature for MVD was developed. This MVD gene score enables the estimation of MVD, reflecting the sensitivity to antiangiogenic inhibitors, in transcriptomic datasets. We demonstrated the utility of the MVD gene score together with a T cell-inflamed gene signature for potential future use as a clinical biomarker.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"398-408"},"PeriodicalIF":2.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor Cell Plasticity and Stromal Microenvironment Distinguish Papillary and Follicular Growth Patterns in a Mouse Model of BRAFV600E-Induced Thyroid Cancer.","authors":"Elin Schoultz, Carmen Moccia, Shawn Liang, Ellen Johansson, Mikael Nilsson","doi":"10.1158/2767-9764.CRC-24-0474","DOIUrl":"10.1158/2767-9764.CRC-24-0474","url":null,"abstract":"<p><strong>Significance: </strong>Cell-of-origin intrinsic features rather than driver mutation identity influence tumor growth patterning in differentiated thyroid cancer and might impact histopathologic diagnosis of thyroid carcinoma subtypes.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"409-421"},"PeriodicalIF":2.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and Antitumor Activity of a Novel aCD25 Treg Depleter RG6292 as a Single Agent and in Combination with Atezolizumab in Patients with Solid Tumors.","authors":"Valentina Gambardella, Michael Ong, Maria E Rodriguez-Ruiz, Jean-Pascal Machiels, Miguel F Sanmamed, Vladimir Galvao, Anna Spreafico, Daniel J Renouf, Stephen J Luen, Rachel Galot, Bernard Doger de Spéville, Emiliano Calvo, Aung Naing, Samira Curdt, Theresa Maria Kolben, Eva Rossmann, Tamara Tanos, Kevin Smart, Maria Amann, Yuying Xie, Linxinyu Xu, Enrique Gomez Alcaide, Nicolas Städler, Nicole Justies, Christophe Boetsch, Vaios Karanikas, Gabriel Schnetzler, Kristoffer S Rohrberg","doi":"10.1158/2767-9764.CRC-24-0638","DOIUrl":"10.1158/2767-9764.CRC-24-0638","url":null,"abstract":"<p><strong>Purpose: </strong>Therapeutic depletion of immunosuppressive regulatory T cells (Treg) may overcome resistance to cancer immunotherapies. RG6292 is an anti-CD25 antibody that preferentially depletes Tregs while preserving effector T-cell functions in preclinical models. The safety, pharmacokinetics, pharmacodynamics, and antitumor efficacy of selective Treg depletion by RG6292 administered as monotherapy or in combination with atezolizumab were evaluated in two phase I studies.</p><p><strong>Patients and methods: </strong>Adult patients with advanced solid tumors were administered intravenous RG6292, given every 3 weeks alone (study 1: NCT04158583, n = 76) or with 1,200 mg atezolizumab every 3 weeks (study 2: NCT04642365, n = 49). Both studies included dose escalation and expansion parts to determine the maximum tolerated dose and recommended phase II dose.</p><p><strong>Results: </strong>RG6292 was well tolerated. Pruritus and rash were the most frequent adverse events and were manageable with supportive treatment. Serum RG6292 levels increased dose proportionally, independent of the atezolizumab combination. RG6292 induced a sustained dose-dependent depletion of peripheral Tregs with no apparent effect on other immune cells. Evidence of intratumoral Treg reduction (≥50% vs. baseline) was observed at RG6292 doses of 35 to 100 mg. The maximum tolerated dose was 165 mg every 3 weeks, and the recommended phase II dose was proposed as 70 mg every 3 weeks. Objective responses were limited to three partial responses in patients receiving RG6292 combined with atezolizumab.</p><p><strong>Conclusions: </strong>RG6292 induced a dose-dependent peripheral blood and measurable intratumoral Treg depletion in concordance with the proposed mode of action; however, clinical efficacy as a single agent or combined with atezolizumab was insufficient to warrant further exploration in this population.</p><p><strong>Significance: </strong>RG6292 (vopikitug) targets CD25 (IL-2Rα) and mediates regulatory T-cell depletion while not interfering with IL-2 signaling. Peripheral and intratumoral Treg depletion was shown in two phase I studies. However, RG6292 alone or in combination with atezolizumab was insufficient to reverse and rescue from established resistance mechanisms in solid tumors.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"422-432"},"PeriodicalIF":2.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11891644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the Radiation Sensitivity Index and 12-Chemokine Gene Expression Signature for Clinical Use in a CLIA Laboratory.","authors":"Anders E Berglund, John Puskas, Sean J Yoder, Andrew T Smith, Douglas C Marchion, Dahui Qin, James J Mulé, Javier F Torres-Roca, Steven A Eschrich","doi":"10.1158/2767-9764.CRC-24-0534","DOIUrl":"10.1158/2767-9764.CRC-24-0534","url":null,"abstract":"<p><strong>Significance: </strong>The RSI and 12CK GES are two GESs that predict tumor radiation sensitivity or the presence of tertiary lymphoid structures in tumors, respectively. These GESs were assessed within the CLIA process for future clinical use. We established proficiency, reproducibility, and reliability characteristics for both signatures in a controlled setting, indicating these GESs are suitable for validation within future clinical trials.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"389-397"},"PeriodicalIF":2.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11873780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Induction of Triple-Negative Breast Cancer Cell Death and Chemosensitivity Using mTORC2-Directed RNAi Nanomedicine.","authors":"Shrusti S Patel, Rebecca S Cook, Justin H Lo, Fiona K Cherry, Ella N Hoogenboezem, Fang Yu, Nora Francini, Nina T Cassidy, Joshua T McCune, Eva F Gbur, Lisa Messier, Thomas A Dean, Kalin L Wilson, Dana M Brantley-Sieders, Craig L Duvall","doi":"10.1158/2767-9764.CRC-24-0261","DOIUrl":"10.1158/2767-9764.CRC-24-0261","url":null,"abstract":"<p><strong>Significance: </strong>We identified an mTORC2/Rictor-directed RNAi nanomedicine that cooperates with chemotherapy to enhance in vivo tumor cell killing in PI3K-active TNBCs.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"458-476"},"PeriodicalIF":2.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"OATP1B-type Transport Function Is a Determinant of Aromatase Inhibitor-Associated Arthralgia Susceptibility.","authors":"Hanieh Taheri, Yang Li, Kevin M Huang, Eman Ahmed, Yan Jin, Thomas Drabison, Yan Yang, Samuel K Kulp, Nicholas A Young, Junan Li, Xiaolin Cheng, Kara N Corps, Christopher C Coss, Jennifer E Vaughn, Maryam B Lustberg, Alex Sparreboom, Shuiying Hu","doi":"10.1158/2767-9764.CRC-24-0475","DOIUrl":"10.1158/2767-9764.CRC-24-0475","url":null,"abstract":"<p><strong>Significance: </strong>AIs are effective but often discontinued because of arthralgia. This study explores the role of OATP1B transporters in AI-related side effects and the potential usage of transporter biomarkers to predict and reduce the risk of arthralgia associated with AI treatment.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"496-510"},"PeriodicalIF":2.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}