Oncoimmunology最新文献

{"title":"Mutant p53-specific CD8TCR-therapy combined with a CD4TCR prevents relapse of cancer and outgrowth of micrometastases.","authors":"Vasiliki Anastasopoulou, Hans Schreiber, Ching-En Lee, Kazuma Kiyotani, Leo Hansmann, Yusuke Nakamura, Matthias Leisegang, Steven P Wolf","doi":"10.1080/2162402X.2025.2514041","DOIUrl":"10.1080/2162402X.2025.2514041","url":null,"abstract":"<p><p>Relapse remains challenging in the treatment of metastatic cancers. More than 50% of human cancers harbor mutant p53 (mp53) as a cancer-specific target. We present the spontaneously metastasizing tumor model Ag104A to advance mp53-specific T cell receptor engineered T cell therapy (TCR-therapy). We identified in Ag104A an autochthonous p53^D256E mutation as neoantigen recognized by a TCR isolated from CD8⁺ T cells (CD8TCR). Cloning of the Ag104A cancer revealed mp53 expression in >99% of cancer cells. Targeting mp53 by CD8TCR-therapy was initially therapeutic, but tumors escaped as cancer cells with reduced or lack of antigen expression. Therefore, we determined whether escape could be prevented by combining the mp53-specific CD8TCR with a CD4⁺ T cell-derived TCR (CD4TCR) recognizing a mutant antigen presented on the stroma of the cancer. No relapse occurred when the mp53-specific CD8TCR was combined with the stroma-recognizing CD4TCR. The combination therapy also prevented the development of macrometastases from cancer cells that had already spread to the lung at the time of TCR-therapy. Macrometastases were only observed after monotherapy. Thus, in a spontaneously metastatic model, tumor relapse and development of macrometastases can be prevented by combining a CD8TCR targeting an autochthonous p53-mutation with a mutation-specific CD4TCR recognizing tumor stroma.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2514041"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12169035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295083","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":"Human cDC1 enhance cytotoxic function of CD226+ terminally exhausted tumor-infiltrating lymphocytes.","authors":"Liam O'Brien, Irina Buckle, Ingrid M Leal-Rojas, Nikita Rosendahl, Kristen J Radford","doi":"10.1080/2162402X.2025.2521391","DOIUrl":"https://doi.org/10.1080/2162402X.2025.2521391","url":null,"abstract":"<p><p>Prevention or reversal of T cell exhaustion is a major objective of cancer immunotherapy. However, few models exist to generate, characterize and modulate exhausted human T cells, particularly within solid tumors <i>in vivo</i>, which likely hampers the discovery and translation of novel therapeutics. In this study we describe a humanized mouse model where functional human CD8+ T cells specific for the tumor antigen NY-ESO-1 develop <i>in vivo</i> from human CD34+ hematopoietic stem cells genetically modified to express a HLA-A *0201-restricted NY-ESO-1 specific T cell receptor (TCR). HLA-A *0201+ NY-ESO-1+ expressing A375 melanoma tumors engrafted in these mice and were refractory to treatment with anti-PD-1 despite being infiltrated with NY-ESO-1 specific T cells. Tumor-Infiltrating Lymphocytes (TIL) upregulated tissue resident memory (TRM) markers CD103 and CD69 along with exhaustion markers PD-1, TIGIT, and CD39 relative to T cells from other organs. Further, TILs failed to secrete cytokines TNF and IFNγ following <i>in vitro</i> stimulation with conventional Type I Dendritic Cells (cDC1), indicative of terminal exhaustion. However, cDC1 stimulation of the terminally exhausted NY-ESO-1 specific TILs led to enhanced tumor killing that was associated with increased CD107a and Granzyme B expression that was restricted to a subset of CD226+ NY-ESO-1 specific TILs. These findings establish a novel platform to investigate T cell exhaustion in human tumors and suggest a role for cDC1 in enhancing terminally exhausted TIL cytotoxic function.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2521391"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144477390","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":"Tumor-infiltrating B cells produce tumor-specific antibodies and may contribute to suppressing tumor in head and neck squamous cell carcinoma.","authors":"Junsei Sameshima, Hu Chen, Naoki Kaneko, Lijing Yan, Shiho Yokomizo, Tomoki Sueyoshi, Haruki Nagano, Taiki Sakamoto, Shoichi Tanaka, Yasuyuki Maruse, Taichi Hattori, Ryoji Kitamura, Yoshikazu Hayashi, Takashi Maehara, Shinsuke Fujii, Tamotsu Kiyoshima, Thomas Guy, Zivile Giedraityte, Wataru Kumamaru, Masafumi Moriyama, Shintaro Kawano","doi":"10.1080/2162402X.2025.2543019","DOIUrl":"https://doi.org/10.1080/2162402X.2025.2543019","url":null,"abstract":"<p><p>The involvement of T cells, particularly cytotoxic T cells, in tumor immunity has been reported, but the roles of B cells and antibodies in tumor immunity remain unclear. Previous studies have primarily focused on circulating B cells in the blood, with limited investigation of tumor-infiltrating B cells (TIL-Bs) and their secreted antibodies in head and neck squamous cell carcinoma (HNSCC) tissue. This study aimed to clarify TIL-Bs' role in HNSCC through comprehensive analyses including single-cell RNA sequencing of 68 cases, B-cell receptor repertoire analysis, multiplex immunofluorescence staining, and spatial transcriptomics analysis of resected HNSCC specimens. We identified CXCL13⁺CD4⁺ T cells that attract B cells, along with TIL-Bs at various differentiation stages, showing clonal expansion of antibody-secreting cells (ASCs). These ASCs exhibited a low somatic hypermutation frequency, indicating that they are likely activated through extrafollicular response rather than germinal center response. Protein microarrays with recombinant antibodies mimicking TIL-Bs secretory antibodies and serum antibodies revealed several antigens highly expressed in tumor cells. These antigens demonstrated higher expression in tumor cells than normal epithelial cells in the resected HNSCC specimens. Tissue analysis indicated that antibodies binding to these antigens are recognized by macrophage and NK cells with Fc receptors, potentially enhancing tumor immunity. The existence of tumor-infiltrating ASCs showed correlation with favorable prognosis. This study demonstrated for the first time that expanded TIL-Bs produce antibodies and likely contribute to tumor elimination by activating tumor immunity in HNSCC tissues. This novel insight could lead to radically new therapies targeting B cells.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2543019"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144800597","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":"Chemoimmunomodulation in triple negative breast cancer: a key to maximizing anti-PD-1 chemoimmunotherapeutic efficacy.","authors":"Mohammed O Gbadamosi, Elizabeth Molchan, Mariana S Makarem, Kennedy L Coleman, Alyssa C Ohaegbulam, Kathleen H Streeks","doi":"10.1080/2162402X.2025.2527303","DOIUrl":"10.1080/2162402X.2025.2527303","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is among the aggressive subtype of breast cancer with a distinct lack of viable treatment strategies and poor clinical outcomes. Anti-PD-1 chemoimmunotherapy (CIT), which leverages the vast array of immunomodulatory effects induced by chemotherapeutic agents to potentiate anti-PD-1 blockade, has emerged as a promising standard-of-care treatment option. However, the clinical benefit from anti-PD-1 CIT has been limited and heterogeneous in advanced TNBC. One of the major reasons for these limitations is the lack of understanding regarding the immunomodulatory properties of chemotherapeutics with respect to individual patients. In this review, we discuss the immunomodulatory properties of first-line chemotherapeutic agents in TNBC and the potential benefits that optimizing chemoimmunomodulation offers toward maximizing CIT efficacy in TNBC.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2527303"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12243914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592699","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":"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":"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":"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}