Oncoimmunology最新文献

{"title":"Patient-specific HLA-I subtypes predict response to immune checkpoint blockade.","authors":"Kyrillus S Shohdy, Jack Atherton, Jessica Longland, Jennifer Alison, Manon Pillai, Fiona Thistlethwaite","doi":"10.1080/2162402X.2025.2462386","DOIUrl":"10.1080/2162402X.2025.2462386","url":null,"abstract":"<p><p>Specific shared HLA-I alleles were linked to the response to immune checkpoint blockade (ICB). We aimed to identify the HLA-A subtypes associated with maximum benefit from ICB. We compiled a clinical dataset of patients who underwent a CLIA-approved germline HLA status testing as part of various advanced immune and cell therapy trials undertaken at the Christie NHS Foundation Trust. A total of 285 patients were eligible for final analysis. We identified 15 HLA-A subtypes, the most common alleles being HLA-A02, HLA-A01, and HLA-A03. A02:01 showed a tumor lineage-specific distribution. One hundred and forty patients received ICB and had evaluable response status. Patients with A01 were associated with better clinical outcomes. No significant associations were observed between HLA-A subtypes and the incidence of immune-related adverse effects. HLA genotyping should be incorporated early in the diagnostic work-up of patients with solid cancers as a predictive and selective biomarker.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2462386"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11849918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143469640","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":"Identification of TTLL8, POTEE, and PKMYT1 as immunogenic cancer-associated antigens and potential immunotherapy targets in ovarian cancer.","authors":"Esen Yonca Bassoy, Remya Raja, Thomas E Rubino, Fabian Coscia, Krista Goergen, Paul Magtibay, Kristina Butler, Alessandra Schmitt, Ann L Oberg, Marion Curtis","doi":"10.1080/2162402X.2025.2460276","DOIUrl":"10.1080/2162402X.2025.2460276","url":null,"abstract":"<p><p>Most high-grade serous ovarian cancers (OC) do not respond to current immunotherapies. To identify potential new actionable tumor antigens in OC, we performed immunopeptidomics on a human OC cell line expressing the HLA-A02:01 haplotype, which is commonly expressed across many racial and ethnic groups. From this dataset, we identified TTLL8, POTEE, and PKMYT1 peptides as candidate tumor antigens with low expression in normal tissues and upregulated expression in OC. Using tissue microarrays, we assessed the protein expression of TTLL8 and POTEE and their association with patient outcomes in a large cohort of OC patients. TTLL8 was found to be expressed in 56.7% of OC and was associated with a worse overall prognosis. POTEE was expressed in 97.2% of OC patients and had no significant association with survival. In patient TILs, increases in cytokine production and tetramer-positive populations identified antigen-specific CD8 T cell responses, which were dependent on antigen presentation by HLA class I. Antigen-specific T cells triggered cancer cell killing of antigen-pulsed OC cells. These findings suggest that TTLL8, POTEE, and PKMYT1 are potential targets for the development of antigen-targeted immunotherapy in OC.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2460276"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075951","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":"Humanized mouse models of <i>KRAS</i>-mutated colorectal and pancreatic cancers with HLA-class-I match for pre-clinical evaluation of cancer immunotherapies.","authors":"Maria E Davola, Olga Cormier, Madeleine Lepard, Jamie McNicol, Susan Collins, Joanne A Hammill, Christopher Silvestri, Jonathan L Bramson, Amy Gillgrass, Karen L Mossman","doi":"10.1080/2162402X.2025.2473163","DOIUrl":"10.1080/2162402X.2025.2473163","url":null,"abstract":"<p><p>Cancer immunotherapy promises to treat challenging cancers including <i>KRAS</i>-mutated colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC). However, pre-clinical animal models that better mimic patient tumor and immune system interactions are required. While humanized mice are promising vehicles for pre-clinical immunotherapy testing, currently used cancer models retain limitations, such as lack of a human thymus for human leukocyte antigen (HLA)-based education of human T cells. As cytotoxic T lymphocyte (CTL) activity underlies many immunotherapies, we developed more clinically relevant <i>KRAS</i>-mutated CRC and PDAC humanized cancer models using transgenic NRG-A2 mice expressing HLA-A2.1 to enable HLA-class-I match between mouse tissues (including the thymus), the humanized immune system and human tumors. Using these novel humanized cancer models and a CTL-mediated combination (immuno)therapy with clinical potential, we were able to recapitulate the complexity and therapy-induced changes reported in patient biopsies, demonstrating the use of these HLA-matched models for pre-clinical validation of novel immunotherapies.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2473163"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525001","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":"Impact of steroid dose and timing on efficacy of combination PD-1/CTLA-4 blockade.","authors":"Nina B Curkovic, Rebecca Irlmeier, Xue Bai, Can Cui, Fei Ye, Hannah R Burnette, Aleigha R Lawless, Juliane Andrade Czapla, Ryan Sullivan, Douglas B Johnson","doi":"10.1080/2162402X.2025.2494433","DOIUrl":"https://doi.org/10.1080/2162402X.2025.2494433","url":null,"abstract":"<p><p>With the increasing use of immune checkpoint inhibitors (ICIs) in combination regimens and in earlier stages of advanced melanoma, the effective management of immune-related adverse events (irAEs) is key to balancing immunotherapy efficacy and toxicity. Conflicting evidence exists on possible detrimental effects of immunosuppression with corticosteroids for irAEs on ICI effectiveness. We conducted a multicenter, retrospective cohort study of immunotherapy-naïve advanced melanoma patients undergoing treatment with ipilimumab and nivolumab and a small cohort treated with nivolumab/relatlimab. We utilized univariate tests to assess response, PFS, and OS based on presence of irAE, receipt of steroids for irAEs, peak dose, and time-to-steroid, as well as multivariable analysis for response, OS, and PFS in patients receiving steroids for irAEs. Among 226 total ipilimumab/nivolumab patients, those without irAEs had poorer PFS and OS compared to irAE groups regardless of steroid administration. In subgroup analysis of patients receiving steroids for an irAE, increased time-to-steroid was significantly associated with improved response (aOR, 1.026 <i>p</i> = 0.0005), PFS (aHR, 0.986 <i>p</i> = 0.001), and OS (aHR, 0.983 <i>p</i> = 0.0008). Higher peak steroid dose was significantly associated with poorer PFS (aHR, 1.002 <i>p</i> = 0.005), and OS (aHR, 1.002 <i>p</i> = 0.003). Use of additional immunosuppressants was associated with poorer OS (aHR, 1.941 <i>p</i> = 0.018). Cumulative dose was not significantly associated with outcomes. Among 42 additional patients treated with nivolumab/relatlimab, irAEs were significantly associated with improved PFS/OS, which appeared to be slightly mitigated by steroid administration; dosing relationships were limited by small numbers.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2494433"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12013437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144053981","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":"Avelumab induces greater Fc-Fc receptor-dependent natural killer cell activation and dendritic cell crosstalk compared to durvalumab.","authors":"Nicole Osborne, Amit Rupani, Vladimir Makarov, Timothy A Chan, Raghvendra M Srivastava","doi":"10.1080/2162402X.2025.2494995","DOIUrl":"https://doi.org/10.1080/2162402X.2025.2494995","url":null,"abstract":"<p><p>Several FDA-approved anti-PD-L1 (programmed cell death ligand-1) monoclonal antibodies (mAbs) are used to treat cancer. While these mAbs primarily target and intercept PD-L1:PD-1 inhibitory signaling in T-cells, the Fc-domains of these mAbs are distinct, and the unique cellular cascades triggered by differing Fc-domains of PD-L1 mAbs have not been directly investigated. In this study, we compared the innate immune effects of two widely used anti-PD-L1 IgG1 mAbs which bear distinct Fc-domains, avelumab (native-Fc) and durvalumab (mutated-Fc), using two-cell and three-cell co-culture systems containing Natural Killer cells (NK-cells), dendritic cells (DCs) and various tumor cell lines of multiple cancer origins. We show a robust enhancement in NK-cell effector function, DC maturation, reciprocal NK:DC crosstalk and DC editing that is unique to avelumab treatment using multiple functional immune assays. By transcriptomic analysis, we show for the first time pivotal differences in gene sets involved in NK-cell effector function, DC maturation, immunoregulatory interactions, and cytokine production between innate immune cells treated with avelumab versus durvalumab. Furthermore, we report several previously unknown Fc-receptor-associated biological pathways uniquely triggered by avelumab. Our findings elucidate novel mechanisms of Fc-dependent actions of PD-L1 mAbs which may inform their use in future clinical trials.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2494995"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12051578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055624","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":"Liver metastases of colorectal cancer contain different subsets of tissue-resident memory CD8 T cells correlated with a distinct risk of relapse following surgery.","authors":"Syrine Abdeljaoued, Alexandre Doussot, Marie Kroemer, Emilien Laloy, Jean René Pallandre, Antoine El Kaddissi, Laurie Spehner, Myriam Ben Khelil, Adeline Bouard, Virginie Mougey, Ugo Chartral, Angélique Vienot, Julien Viot, Zaher Lakkis, Franck Monnien, Romain Loyon, Christophe Borg","doi":"10.1080/2162402X.2025.2455176","DOIUrl":"10.1080/2162402X.2025.2455176","url":null,"abstract":"<p><p>Tissue-resident memory (T_RM) T cells have emerged as key players in cancer immunosurveillance, and their presence has been linked to a favorable clinical outcome in solid cancer patients. Liver metastases exhibit a highly immunosuppressive tumor microenvironment, however, the role and clinical impact of T_RM cell infiltration in colorectal cancer remain elusive. The expression of several tissue residency and activation biomarkers has been investigated on tumor-infiltrating lymphocytes isolated from 26 patients' colorectal cancer liver metastases (CRC liver metastases) and compared to 16 peripheral blood samples of patients with CRC liver metastases. Cytokine production was also evaluated in <i>in vitro-activated</i> T_RM and non-T_RM cells. The prognostic value of T_RM cells was also assessed in a well-defined cohort of CRC liver metastases. Here we identified two subsets of T_RM cells expressing CD103 and/or CD69 showing significantly higher expression of tissue residency and activation biomarkers. CD103⁺CD69⁺ T_RM cells subset showed almost exclusive expression of tumor reactivity biomarkers PD-1 and CD39. Supporting this observation, CD103⁺CD69⁺ T_RM cells showed a more oligoclonal TCR repertoire. Both T_RM subsets presented higher cytotoxic and functional capacity compared to non-T_RM cells. Our study shows that only the presence of CD103⁺CD69⁺ T_RM cells is associated with longer recurrence-free survival of colorectal cancer patients with liver metastases. Taken together, our work demonstrates the existence of a phenotypic heterogeneity of T_RM cells in colorectal cancer liver metastases. In this study, we identified a population of CD103⁺CD69⁺ T_RM cells exhibiting the characteristics of tumor reactivity and correlated with better patients' prognosis, with potential implications in optimal therapeutic strategies determination.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2455176"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061136","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":"Combined tumor-associated microbiome and immune gene expression profiling predict response to neoadjuvant chemo-radiotherapy in locally advanced rectal cancer.","authors":"Raffaello Roesel, Francesco Strati, Camilla Basso, Samantha Epistolio, Paolo Spina, Julija Djordjevic, Elisa Sorrenti, Martina Villa, Agnese Cianfarani, Francesco Mongelli, Jacopo Galafassi, Sotirios G Popeskou, Federica Facciotti, Cecilia Caprera, Federica Melle, Pietro Edoardo Majno-Hurst, Alessandra Franzetti-Pellanda, Sara De Dosso, Ferdinando Bonfiglio, Milo Frattini, Dimitrios Christoforidis, Giandomenica Iezzi","doi":"10.1080/2162402X.2025.2465015","DOIUrl":"10.1080/2162402X.2025.2465015","url":null,"abstract":"<p><p>Locally advanced rectal cancer (LARC) is treated with neoadjuvant chemo-radiotherapy (nCRT) followed by surgery. A minority of patients show complete response (CR) to nCRT and may avoid surgery and its functional consequences. Instead, most patients show non-complete response (non-CR) and may benefit from additional treatments to increase CR rates. Reliable predictive markers are lacking. Aim of this study was to identify novel signatures predicting nCRT responsiveness. We performed a combined analysis of tumor-associated microbiome and immune gene expression profiling of diagnostic biopsies from 70 patients undergoing nCRT followed by rectal resection, including 16 with CR and 54 with non-CR. Findings were validated by an independent cohort of 49 patients, including 7 with CR and 42 with non-CR. Intratumoral microbiota significantly differed between CR and non-CR groups at genus and species level. Colonization by bacterial species of <i>Ruminococcus</i> genera was consistently associated with CR, whereas abundance of <i>Fusobacterium</i>, <i>Porhpyromonas</i>, and <i>Oscillibacter</i> species predicted non-CR. Immune gene profiling revealed a panel of 59 differentially expressed genes and significant upregulation of IFN-gamma and -alpha response in patients with CR. Integrated microbiome and immune gene profiling analysis unraveled clustering of microbial taxa with each other and with immune cell-related genes and allowed the identification of a combined signature correctly identifying non-CRS in both cohorts. Thus, combined intratumoral microbiome-immune profiling improves the prediction of response to nCRT. Correct identification of unresponsive patients and of bacteria promoting responsiveness might lead to innovative therapeutic approaches based on gut microbiota pre-conditioning to increase nCRT effectiveness in LARC.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2465015"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484244","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":"Co-targeting of VEGFR2 and PD-L1 promotes survival and vasculature normalization in pleural mesothelioma.","authors":"Sophie Rovers, Jonas Van Audenaerde, Ruben Verloy, Jorrit De Waele, Louize Brants, Christophe Hermans, Ho Wa Lau, Céline Merlin, Maria Möller Ribas, Peter Ponsaerts, Steven Van Laere, Filip Lardon, An Wouters, Scott A Fisher, Jan van Meerbeeck, Elly Marcq, Evelien Smits","doi":"10.1080/2162402X.2025.2512104","DOIUrl":"10.1080/2162402X.2025.2512104","url":null,"abstract":"<p><p>Pleural mesothelioma (PM) is an aggressive cancer caused by asbestos exposure, with limited treatment options and poor prognosis, highlighting the need for more effective therapies. Combining immune checkpoint blockade with anti-angiogenic therapy has shown potential in other cancers. Our study investigated the combined inhibition of PD-L1 and VEGFR2 in a mouse model of PM. Using C57BL/6 mice with subcutaneous AE17 mesothelioma tumors, we assessed the effects of anti-PD-L1 therapy with induction, concomitant, or consolidation anti-VEGFR2 treatment. Mice received intraperitoneal doses every three days for three treatments. Tumor growth, survival, tumor-infiltrating immune cells and intra-tumoral vasculature were analyzed. Results demonstrated that combining anti-PD-L1 with induction or concomitant anti-VEGFR2 significantly delayed tumor growth, improved survival, and promoted vascular maturation. Flow cytometry suggested T cell exhaustion in monotherapy groups, while no significant changes were seen with concomitant treatment. Depleting CD4⁺ T cells reversed the positive effects of concomitant treatment. These findings suggest that dual inhibition of PD-L1 and VEGFR2 is a promising therapeutic approach for PM, with CD4⁺ T cells playing a critical role in the immune response. This dual targeting of immune checkpoints and angiogenesis offers a potential new avenue for improving outcomes in PM treatment and warrants further clinical exploration.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2512104"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12123973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144175355","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 combination of body mass index and serum creatinine levels predicts survival in patients with Hodgkin lymphoma treated with nivolumab in the CheckMate 205 study.","authors":"Rosaria De Filippi, Fortunato Morabito, Giovanni Tripepi, Stephen M Ansell, Sara Mele, Emanuela Morelli, Domenico Mallardo, Daniela Donnarumma, Francesco Volzone, Alev Akyol, Annarosa Cuccaro, Mariangela Saggese, Matteo Bonanni, Maria Esposito, Stefania Crisci, Pier Luigi Zinzani, Antonio Pinto","doi":"10.1080/2162402X.2025.2513106","DOIUrl":"https://doi.org/10.1080/2162402X.2025.2513106","url":null,"abstract":"<p><p>Patients with solid tumors and a higher body mass index (BMI) experience improved survival after receiving anti-PD1 antibodies. The predictive role of BMI in Hodgkin Lymphoma (HL), the most sensitive malignancy to PD1-blockade, remains unclear. We analyzed the association between BMI and survival outcomes in patients treated with the anti-PD-1 antibody nivolumab within the CheckMate 205 study. Patients with a lower BMI (<24.03 kg/m²) had a longer progression-free survival (PFS) (46.4% at three years) than those with a higher BMI (≥24.03 kg/m²;19.6%; <i>p</i> = 0.03). Combining the BMI cutoff with serum creatinine (sCr) levels generated a variable (BMCI) stratifying patients into distinct PFS risk groups. Patients with a BMCI^high (BMI ≥24.03 kg/m²/sCr <0.7 mg/dL) displayed a threefold increased PFS risk (95% CI,1.6-5.7; <i>p</i> < 0.001) than those with a BMCI^low (BMI <24.03 kg/m²/sCr ≥0.7 mg/dL). In a separate analysis of pretreated patients, those with a BMCI^high had a PFS risk 3.5-fold higher (95% CI,1.9-6.6; <i>p</i> < 0.001) than patients with a BMCI^low. The BMCI maintained its independent significance in a multivariable model including attenuating factors and predictive biomarkers. HL patients with reduced BMI but preserved lean body mass (BMCI^low) exhibit a more favorable response to nivolumab. Results highlight an unexpected side of the 'obesity paradox' in HL.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2513106"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200576","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":"Peripheral memory B cell population maintenance and long-term survival after perioperative chemoimmunotherapy in NSCLC (NADIM trial).","authors":"Belén Sierra Rodero, Cristina Martínez-Toledo, Ernest Nadal, Marta Molina-Alejandre, Rosario García Campelo, Ángeles Gil-González, Bartomeu Massuti, Aránzazu García-Grande, Manuel Dómine, Amelia Insa, Javier de Castro Carpeño, Gerardo Huidobro Vence, Margarita Majem, Alex Martinez-Marti, Diego Megias, Daniel Lobato, Ana Collazo-Lorduy, Virginia Calvo, Mariano Provencio, Alberto Cruz-Bermúdez","doi":"10.1080/2162402X.2025.2513109","DOIUrl":"https://doi.org/10.1080/2162402X.2025.2513109","url":null,"abstract":"<p><p>Perioperative chemoimmunotherapy has significantly improved survival rates for non-small cell lung cancer (NSCLC). However, current tissue biomarkers remain inadequate, underscoring the need for more sensitive and accessible alternatives to monitor relapse risk. Intratumoral B-cells are increasingly recognized for their role in enhancing immunotherapy outcomes, yet the contribution of peripheral B-cells to immune surveillance remains unexplored. Peripheral B-cell immunophenotypes were analyzed from blood samples (at diagnosis, post-neoadjuvant, and at 6- and 12-months of adjuvant treatment) in 41 stage IIIA NSCLC patients treated with perioperative nivolumab plus chemotherapy, included in the NADIM clinical trial (NCT03081689). Results were correlated with 5-year survival outcomes and validated through unsupervised clustering. An increase in the percentage of total B-cells (CD19⁺CD20⁺) and naïve B-cells (CD19⁺CD20⁺CD24⁺CD38⁺CD27^-CD10^-), along with a reduction in CD20 expression on total B-cells, a decrease in the proportion of memory B-cells (CD19⁺CD20⁺CD24⁺CD38^-/lowCD27⁺) and transitional B-cells (CD19⁺CD20⁺CD24⁺⁺CD38⁺⁺CD10⁺), was observed during the time encompassed between the end of neoadjuvant treatment and the posterior 6 months of adjuvant treatment. Higher levels of CD20 expression on total B-cells, along with an increased percentage of memory B-cells, or activated B-cells (CD19⁺CD20⁺CD25⁺), at 6- and 12-months of adjuvant treatment, were associated with increased survival. Conversely, higher levels of a newly described circulating population of CD19⁺CD20^lowCD25^lowCD27^low B-cells during adjuvant treatment were linked to disease progression. Perioperative nivolumab plus chemotherapy in resectable NSCLC patients induces significant changes in peripheral B-cells. The persistence of circulating memory B-cells during adjuvant treatment might play a crucial role in survival.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2513109"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144227269","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}