Oncoimmunology最新文献

{"title":"How macrophages use extracellular calreticulin to chase their prey.","authors":"Liwei Zhao, Peng Liu, Oliver Kepp, Guido Kroemer","doi":"10.1080/2162402X.2025.2533494","DOIUrl":"10.1080/2162402X.2025.2533494","url":null,"abstract":"<p><p>Recent findings reveal that macrophages actively control clearance by desialylating target cells via NEU1 and releasing cathepsin-cleaved calreticulin (CALR) to mark them for phagocytosis. This uncovers a dual role for CALR as immune activator or repressor, depending on its form and context, with distinct implications for cancer immunity.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2533494"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12258218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144620862","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":"Chronic antigen stimulation in melanoma induces T cell exhaustion and limits efficacy of T cell bispecific therapies.","authors":"Idil Hutter-Karakoc, Eleni Maria Varypataki, Aparna Neelakandhan, Simone Lang, Vesna Kramar, Ahmet Varol, Sasha Simons, Marine Richard, Mudita Pincha, Dario Venetz, Johannes Sam, Nicole Joller, Christian Münz, Pablo Umana, Christian Klein, Maria Amann","doi":"10.1080/2162402X.2025.2526444","DOIUrl":"10.1080/2162402X.2025.2526444","url":null,"abstract":"<p><p>T cell bispecific antibodies (TCBs) have demonstrated promising results in patients with solid tumors, yet the immunological mechanisms influencing their efficacy require further investigation. T cell exhaustion, induced by prolonged antigen exposure, is known to compromise T cell-based immunotherapies, but its effect on TCB efficacy remains unclear. Herein, we assessed the TCB efficacy on tumor-specific T cells, emphasizing their functional status. Utilizing an immunocompetent mouse model with melanoma expressing an immunogenic antigen, we showed that tumor-specific T cells acquire an exhausted phenotype and fail to expand under TCB treatment. Both mouse and human tumor-specific T cells <i>in vitro</i> demonstrated that chronically stimulated T cells exhibit a reduced response to TCBs. The comparison of TCB efficacy in T cell-inflamed versus non-inflamed tumors in mice revealed TCB success depends more on T cell functional fitness than their initial abundance. These data underscore the importance of T cell exhaustion, suggesting that exhausted tumor-specific T cells are unlikely to be the primary effectors redirected by TCBs for tumor eradication. Our study highlights the need to maintain T cell fitness and prevent exhaustion to enhance TCB therapy outcomes, which may help identify patients who could benefit most from TCB treatments in clinics.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2526444"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12382474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144975219","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":"A phase 2 trial of CXCR4 antagonism and PD1 inhibition in metastatic pancreatic adenocarcinoma reveals recruitment of T cells but also immunosuppressive macrophages.","authors":"Katherine M Bever, Sarah M Shin, Jennifer N Durham, Hanfei Qi, Alexei Hernandez, Erin M Coyne, Nicole E Gross, Soren Charmsaz, Jayalaxmi Suresh Babu, Diana Carolina Vargas Carvajal, Rohan Verma, Yanyi Sun, Zhehao Zhang, Xuan Yuan, Courtney D Cannon, Sarah N Hughes, Sarah Mitchell, Madeline Figlewski, James M Leatherman, Hao Wang, Robert A Anders, Elizabeth M Jaffee, Dung T Le, Won Jin Ho","doi":"10.1080/2162402X.2025.2543614","DOIUrl":"10.1080/2162402X.2025.2543614","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is characterized by dense stroma and myeloid-rich microenvironment that confer resistance to immunotherapies. Previous studies demonstrated that disrupting the immune-stroma CXCR4-CXCL12 axis facilitates T cell recruitment and mobility to collaborate with anti-PD1/PD-L1 therapy. We sought to test the clinical viability of this immunotherapeutic strategy. 21 patients with metastatic PDAC were enrolled and treated in a phase 2 trial evaluating the effects of the plerixafor/AMD3100 and cemiplimab. Primary endpoint was objective response rate. Blood and tissue biospecimens were collected for correlative analyses. Parallel mouse studies were used to determine potential mechanisms of resistance. Treatments were well-tolerated, but only two patients demonstrated a best response of stable disease. Correlative analyses confirmed significant mobilization of immune cells into circulation as well as increased immune infiltration into the tumor. High-parameter imaging revealed higher levels of CD8⁺ T cells but also granulocytes and macrophages upon treatment. Spatial analysis showed that treatment resulted in closer proximity between macrophages and T cells but not between granulocytes and T cells. Mouse studies revealed that whereas total granulocyte depletion had no effect on immunotherapeutic efficacy, macrophage-targeting yielded significant benefit. Tumor growth measurements and immune profiling of immunotherapeutic combinations incorporating macrophage-targeting showed that despite the increased T cell infiltration, CXCR4 antagonism was in fact associated with enrichment of CD206^hiIA/IE^lo macrophage subtypes and modestly dampened efficacy. Our findings validate the utility of CXCR4 antagonism as an effective immune-recruiting platform but also underscores the need for strategies that better leverage its effects.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2543614"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12360203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859817","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":"The immune checkpoint LAG-3 is expressed by melanoma cells and correlates with clinical progression of the melanoma.","authors":"Melanie Wiecken, Devayani Machiraju, Shounak Chakraborty, Eva-Maria Mayr, Bénédicte Lenoir, Rosa Eurich, Jasmin Richter, Nicole Pfarr, Niels Halama, Jessica C Hassel","doi":"10.1080/2162402X.2024.2430066","DOIUrl":"https://doi.org/10.1080/2162402X.2024.2430066","url":null,"abstract":"<p><p>Immune checkpoint blockers have substantially improved prognosis of melanoma patients, nevertheless, resistance remains a significant problem. Here, intrinsic and extrinsic factors in the tumor microenvironment are discussed, including the expression of alternative immune checkpoints such as lymphocyte activation gene 3 (LAG-3) and T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3). While most studies focus on immune cell expression of these proteins, we investigated their melanoma cell intrinsic expression by immunohistochemistry in melanoma metastases of 60 patients treated with anti-programmed cell death protein 1 (PD-1) and/or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) therapy, and correlated it with the expression of potential ligands, RNA sequencing data and clinical outcome. LAG-3 and TIM-3 were commonly expressed in melanoma cells. In the stage IV cohort, expression of LAG-3 was associated with M1 stage (<i>p</i> < 0.001) and previous exposure to immune checkpoint inhibitors (<i>p</i> = 0.029). Moreover, in the anti-PD-1 monotherapy treatment group patients with high LAG-3 expression by tumor cells tended to have a shorter progression-free survival (<i>p</i> = 0.088), whereas high expression of TIM-3 was associated with a significantly longer overall survival (<i>p</i> = 0.007). In conclusion, we provide a systematic analysis of melanoma cell intrinsic LAG-3 and TIM-3 expression, highlighting potential implications of their expression on patient survival.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2430066"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883141","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":"Surrogate markers of intestinal dysfunction associated with survival in advanced cancers.","authors":"Roxanne Birebent, Damien Drubay, Carolina Alves Costa Silva, Federica Marmorino, Giacomo Vitali, Gianmarco Piccinno, Yoan Hurtado, Adele Bonato, Lorenzo Belluomini, Meriem Messaoudene, Bertrand Routy, Marine Fidelle, Gerard Zalcman, Julien Mazieres, Clarisse Audigier-Valette, Denis Moro-Sibilot, François Goldwasser, Arnaud Scherpereel, Hervé Pegliasco, François Ghiringhelli, Anna Reni, Fabrice Barlesi, Laurence Albiges, David Planchard, Stéphanie Martinez, Benjamin Besse, Nicola Segata, Chiara Cremolini, Laurence Zitvogel, Valerio Iebba, Lisa Derosa","doi":"10.1080/2162402X.2025.2484880","DOIUrl":"10.1080/2162402X.2025.2484880","url":null,"abstract":"<p><p>Deviations in the diversity and composition of the gut microbiota are called \"gut dysbiosis\". They have been linked to various chronic diseases including cancers and resistance to immunotherapy. Stool shotgun based-metagenomics informs on the ecological composition of the gut microbiota and the prevalence of homeostatic bacteria such as <i>Akkermansia muciniphila (</i>Akk), while determination of the serum addressin MAdCAM-1 instructs on endothelial gut barrier dysfunction. Here we examined patient survival during chemo-immuno-therapy in 955 cancer patients across four independent cohorts of non-small cell lung (NSCLC), genitourinary (GU) and colorectal (CRC) cancers, according to hallmarks of gut dysbiosis. We show that Akk prevalence represents a stable and favorable phenotype in NSCLC and CRC cancer patients. Over-dominance of Akk above the healthy threshold was observed in dismal prognosis in NSCLC and GU and mirrored an immunosuppressive gut ecosystem and excessive intestinal epithelial exfoliation in NSCLC. In CRC, the combination of a lack of Akk and low sMAdCAM-1 levels identified a subset comprising 28% of patients with reduced survival, independent of the immunoscore. We conclude that gut dysbiosis hallmarks deserve integration within the diagnosis toolbox in oncological practice.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2484880"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796265","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":"Evaluating the effect of immune checkpoint inhibitor treatment on chronic obstructive pulmonary disease in lung cancer patients.","authors":"Anet Greib, Songzhu Zhao, Michelle Ploch, Jonathan Henricks, Robert Easterling, Meghana Moodabagil, Gabrielle Lopez, Mingjia Li, Evelyn G Goodyear, John Sharp, Asrar Alahmadi, Jacob Kaufman, Regan Memmott, Kai He, Peter Shields, David P Carbone, Gregory A Otterson, Carolyn J Presley, Lai Wei, Dwight H Owen, Kevin Ho","doi":"10.1080/2162402X.2025.2469375","DOIUrl":"10.1080/2162402X.2025.2469375","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) are first line treatment for advanced lung cancer. Tobacco use is a shared risk factor for lung cancer and chronic obstructive pulmonary disease (COPD). Although many patients with COPD and lung cancer receive ICIs, the impact of ICIs on COPD is unknown. Here, we evaluated whether ICI treatment was associated with increased COPD disease burden. We conducted a retrospective cohort study of lung cancer patients with and without preexisting COPD who received ICIs from 2011-2021 at The Ohio State University (OSU). For all patients, number of steroid courses and respiratory related hospitalizations were recorded. For those with COPD, COPD medications were collected at and after ICI initiation. Pulmonary function tests, COPD exacerbations, and COPD-related hospitalizations were compared before and after ICI treatment. Linear and generalized mixed models were used to account for potential confounders of worsening COPD. Among 1083 lung cancer patients who received ICIs, 585 (54.0%) had pre-ICI COPD. Patients with COPD were prescribed more COPD medications (3 [1, 4] vs 1 [0, 3], <i>p</i> < 0.001), had more COPD exacerbations (38.3% vs 25.8%, <i>p</i> < 0.001), and more COPD-related hospitalizations (27.9% vs 16.9%, <i>p</i> < 0.001) after ICI initiation compared to before. These findings persisted after multivariable analysis controlling for patients who received chemotherapy or chemoradiation within 12 months of ICI initiation, cancer type, age, BMI, sex, smoking status, type of ICI, and number of ICI doses (<i>p</i> < 0.001). This is a comprehensive study that describes lung cancer patients with COPD treated with ICIs have increased COPD disease burden after ICI initiation.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2469375"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11849934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143469637","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":"Mixed cryoglobulinemia decelerates hepatocellular carcinoma development in hepatitis C patients with SVR by downregulating regulatory B cells: a 12-year prospective cohort study.","authors":"Ming-Ling Chang, Jur-Shan Cheng, Wei-Ting Chen, Yi-Jyun Shen, Chia-Jung Kuo, Rong-Nan Chien","doi":"10.1080/2162402X.2025.2470128","DOIUrl":"10.1080/2162402X.2025.2470128","url":null,"abstract":"<p><p>How mixed cryoglobulinemia (MC) affects cancer risk in chronic hepatitis C patients with sustained virologic response (SVR) remains unclear. In a 12-year prospective study, post-SVR MC was assessed every 3‒6 months. Among the 891 SVR patients, 265 (29.7%) had baseline (24 weeks after completing anti-HCV therapy) MC, and the 12-year cancer cumulative incidence was 19.7%. Among the 73 patients who developed cancer, 37 (50.7%) had hepatocellular carcinoma (HCC), with the following associated baseline variables: for cancer, male sex, age and alanine aminotransferase (ALT) levels; for HCC, male sex, age, and cirrhosis; and for non-HCC cancer, rheumatoid factor levels. Among patients with post-SVR HCC, the mean time to HCC was longer in those with than in those without baseline MC (1545.4 ± 276.5 vs. 856.9 ± 115.2 days, <i>p</i> = 0.014). Patients with baseline MC had decreased circulating interleukin-10 (IL-10)-positive B cell (CD19+IL-10+cells/CD19+cells) (31.24 ± 16.14 vs. 40.08 ± 15.42%, <i>p</i> = 0.031), regulatory B cell (Breg) (CD19+CD24hi CD27+cells/CD19+cells) (10.45 ± 7.10 vs. 15.76 ± 9.14%, <i>p</i> = 0.035), IL-10-positive Breg (CD19+CD24hiCD27+IL-10+cells/CD19+cells) (5.06 ± 4.68 vs. 8.83 ± 5.46%, <i>p</i> = 0.015) and HCC-infiltrating Breg (18.6 ± 10 vs. 33.51 ± 6.8%, <i>p</i> = 0.022) ratios but comparable circulating and HCC-infiltrating regulatory T cell ratios relative to patients without baseline MC. In conclusion, old male SVR patients with elevated ALT levels or cirrhosis require intensive monitoring for cancer development, especially HCC. Tailored HCC follow-up is needed for SVR patients according to their baseline MC, which might downregulate Bregs to decelerate HCC development for almost 2 years.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2470128"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11866965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143505182","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":"Loss of the extracellular protease ADAMTS1 reveals an antitumorigenic program involving the action of NIDOGEN-1 on macrophage polarization.","authors":"Rita Caracuel-Peramos, Francisco Javier Rodríguez-Baena, Silvia Redondo-García, Juan Antonio Villatoro-García, Ana García-Muñoz, Carlos Peris-Torres, María Del Carmen Plaza-Calonge, Alba Rubio-Gayarre, Belén López-Millán, Carmela Ricciardelli, Darryl L Russell, Pedro Carmona-Sáez, Juan Carlos Rodríguez-Manzaneque","doi":"10.1080/2162402X.2025.2508057","DOIUrl":"10.1080/2162402X.2025.2508057","url":null,"abstract":"<p><p>Recent research highlighted the contribution of extracellular matrix, and particularly of ADAMTS proteases, in immune regulation. Now, our work with melanoma and mammary tumor models revealed that tumor blockade induced by the lack of <i>Adamts1</i> led to an increased vascular deposition of its substrate, the basement membrane glycoprotein NIDOGEN-1 (NID1). Significantly, the overexpression of NID1 in the melanoma syngeneic model also blocked tumor progression, disclosing an overlapping phenotype with the absence of <i>Adamts1</i>. These tumors showed important alterations in their immune infiltrates, emphasizing an enhanced presence of antitumorigenic macrophages and a global inflammatory landscape. We corroborated <i>in vitro</i> that full length NID1, but not its fragments, promoted an M1-like macrophage polarization, mainly mediated by the αvβ3 integrin. Significantly, the projection of RNA-seq from our tumor models to two large human melanoma datasets allowed us to discover a new gene signature associated with good prognosis and the abundance of M1-like macrophages. These results support NID1 as a novel tumor suppressor with immunomodulatory properties, and unveil the existence of key oncological drivers in the extracellular scenario.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2508057"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144121200","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":"Increasing the odds: antibody-mediated delivery of two distinct immunogenic T-cell epitopes with one antibody.","authors":"Willemijn van der Wulp, Dennis F G Remst, Carli S Koster, Anne K Wouters, Maaike E Ressing, Janine Schuurman, Sander I van Kasteren, Boris Bleijlevens, Rob C Hoeben, Lars Guelen, Mirjam H M Heemskerk","doi":"10.1080/2162402X.2025.2508050","DOIUrl":"10.1080/2162402X.2025.2508050","url":null,"abstract":"<p><p>Antibody-epitope conjugates (AECs) proved to be a promising new therapeutic strategy to redirect virus-specific CD8⁺ T cells toward cancer cells by delivering T-cell epitopes. To be able to redirect a larger fraction of the virus-specific T-cell population, it is beneficial to deliver a broader selection of T-cell epitopes. We investigated two different methods to generate AECs with two distinct virus-specific T-cell epitopes fused to one antibody. Epitopes were either placed in a tandem-like fashion at the C-terminus of the AEC (t-AEC) or bispecific-AECs (bs-AECs) were generated via controlled Fab-arm exchange to generate bs-AECs with two identical antigen binding domains, but two distinct epitopes on each Fab-arm. Our study revealed that maintaining a free epitope terminus was required for efficient delivery of the virus-specific T-cell epitopes. Consequently, viral-epitope delivery using t-AECs was suboptimal as the concatenated epitopes were less effectively delivered to the target cells. However, well-defined bs-AECs containing both CMV and EBV epitopes were successfully generated and both <i>in vitro</i> and <i>in vivo</i> efficacy was evaluated. Our results demonstrate that bispecific-AECs can efficiently deliver EBV and CMV epitopes simultaneously to multiple cancer cell lines from different origins, thereby redirecting and activating two distinct populations of virus-specific T cells. Furthermore, our <i>in vivo</i> findings indicate that when both virus-specific T-cell populations are present and tumor cells express the proteases required for efficient epitope delivery, bs-AECs exhibit similar efficacy in reducing tumor burden compared to AECs. To conclude, our study demonstrates the feasibility of redirecting two groups of virus-specific T cells using a single antibody and highlights the potential of bs-AECs both <i>in vitro</i> and <i>in vivo</i>.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2508050"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12118402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144163150","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":"CD200 immune checkpoint expression is associated with inferior outcome in multiple myeloma patients treated with anti-CD38 monoclonal antibodies.","authors":"Djamila Chemlal, Camille Pochard, Valentin Jacquier, Angélique Bruyer, Ludovic Gabellier, Léa Fornero, Clément Vempère, Amélie Machura, Guilhem Requirand, Nicolas Robert, Caroline Bret, Guillaume Cartron, Laure Vincent, Hugues de Boussac, Jérôme Moreaux, Charles Herbaux","doi":"10.1080/2162402X.2025.2532226","DOIUrl":"10.1080/2162402X.2025.2532226","url":null,"abstract":"<p><p>In multiple myeloma (MM), the anti-CD38 monoclonal antibody Daratumumab has become essential in the therapeutic arsenal, although very few predictive factors of response to Daratumumab have been identified in clinical studies. We have prospectively collected biological data from 97 patients treated with Daratumumab in first line or at relapse in our center between 2016 and 2020. These data included multiparameter flow cytometry phenotype (CD200, CD117, CD56, CD38, CD45, and CD27), cytogenetic, and transcriptomic gene expression profiling (GEP) of tumor plasma cells before treatment with Daratumumab. We first looked for predictive factors of response to Daratumumab. We found that high CD56 expression and CD45 expression were significantly associated with better progression free survival (PFS) whereas high CD200 expression was significantly associated with poorer PFS. Then, we showed that the CD200-CD200R immune synapse is responsible for a decrease in Daratumumab response through the alteration of NK cells' activity. Finally, we demonstrated that inhibition of CD200 increase response to Daratumumab in MM patient samples, highlighting its potential as a predictive biomarker for Daratumumab response and as a possible therapeutic target in combination with Daratumumab. This study is the first to identify phenotypic and molecular factors' predictor of response to Daratumumab.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2532226"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12283004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668730","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}