Oncoimmunology最新文献

{"title":"Circulating cytokine associations with clinical outcomes in melanoma patients treated with combination nivolumab plus ipilimumab.","authors":"Jiajia Chen, Giuseppe Tarantino, Mariano Severgnini, Joanna Baginska, Anita Giobbie-Hurder, Jason L Weirather, Michael Manos, Janice D Russell, Kathleen L Pfaff, Scott J Rodig, Amy Y Huang, Ryan Brennick, Matthew Nazzaro, Emma Hathaway, Marta Holovatska, Claire Manuszak, Srinika Ranasinghe, David Liu, F Stephen Hodi","doi":"10.1080/2162402X.2024.2432723","DOIUrl":"10.1080/2162402X.2024.2432723","url":null,"abstract":"<p><p>Nivolumab plus ipilimumab (aCTLA-4/aPD-1) combination therapy has significantly improved clinical outcomes in patients with metastatic melanoma, with 50%-60% of patients responding to treatment, but predictors of response are poorly characterized. We hypothesized that circulating cytokines and peripheral white blood cells may predict response to therapy and evaluated 15 cytokines and complete blood counts (CBC with differentials) from 89 patients with advanced melanoma treated with combination therapy from three points in time: pre-treatment, one month and approximately three months after starting therapy. Clinical endpoints evaluated included durable clinical benefit (DCB), progression-free survival (PFS), and overall survival (OS). A parsimonious predictive model was developed to identify cytokines predictors of response to combination therapy. In this study, we found that pre-treatment, patients with DCB had higher IL-23, lower CXCL6, and lower IL-10 levels. Lower NLR one month after starting therapy predicted better PFS and OS, primarily driven by an increase in absolute lymphocytes. A multivariate model demonstrated that baseline CXCL6, IL-10, IL-23 were independent predictors of therapy response, and the combined model has reached an area under the curve (AUC) of 0.79 in prediction of response to combination therapy. Our study identified baseline CXCL6, IL-23, and IL-10 as predictors of response to aCTLA4/aPD1 combination therapy among patients with metastatic melanoma. This study also provides a framework for identifying patients who are likely to respond to combination ICB, as well as a subset of patients with high risk of developing resistance and are thus in need of alternative therapeutic options, such as clinical trials.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2432723"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856325","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":"Induction of cell death in malignant cells and regulatory T cells in the tumor microenvironment by targeting CD137.","authors":"Rui Sun, Kang Yi Lee, Yu Mei, Emily Nickles, Jia Le Lin, Runze Xia, Haiyan Liu, Herbert Schwarz","doi":"10.1080/2162402X.2024.2443265","DOIUrl":"https://doi.org/10.1080/2162402X.2024.2443265","url":null,"abstract":"<p><p>Regulatory T cells (Tregs) contribute significantly to the immunosuppressive nature of the tumor microenvironment which is a main barrier for immunotherapies of solid cancers. Reducing Treg numbers enhances anti-tumor immune responses but current depletion strategies also impair effector T cells (Teffs), potentially leading to reduced anti-tumor immunity and/or autoimmune diseases. CD137 has been identified as the most differentially expressed gene between peripheral Tregs and intratumoral Tregs in virtually all solid cancers. Further, CD137 is expressed by malignant cells of certain cancers, making it a potential target for tumor immunotherapy. Here, we report the development of a fully human anti-human CD137 antibody of the IgG1 isotype, clone P1A1, that induces antibody-dependent cell-mediated cytotoxicity (ADCC) in CD137⁺ Tregs and cancer cells. P1A1 cross-reacts with murine CD137 which allowed testing murine chimeric P1A1 in syngeneic murine tumor models where P1A1 significantly reduced the number of CD137⁺ Tregs and inhibited tumor growth in a murine hepatocellular carcinoma (HCC) and a melanoma lung metastasis model. P1A1 can also be internalized thus enabling it as a carrier for drugs to target CD137⁺ Tregs and cancer cells. These anti-cancer properties suggest a translation of P1A1 to human immunotherapy.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2443265"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883138","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":"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":"Pushing the boundaries of radiotherapy-immunotherapy combinations: highlights from the 7^th immunorad conference.","authors":"Pierre-Antoine Laurent, Fabrice André, Alexandre Bobard, Desiree Deandreis, Sandra Demaria, Stephane Depil, Stefan B Eichmüller, Cristian Fernandez-Palomo, Floris Foijer, Lorenzo Galluzzi, Jérôme Galon, Matthias Guckenberger, Kevin J Harrington, Fernanda G Herrera, Peter E Huber, Antoine Italiano, Sana D Karam, Guido Kroemer, Philippe Lambin, Carola Leuschner, Alberto Mantovani, Etienne Meylan, Michele Mondini, Mikael J Pittet, Jean-Pierre Pouget, Jordi Remon, Claus S Sørensen, Christos Sotiriou, Claire Vanpouille-Box, Ralph R Weichselbaum, James W Welsh, Laurence Zitvogel, Silvia C Formenti, Eric Deutsch","doi":"10.1080/2162402X.2024.2432726","DOIUrl":"https://doi.org/10.1080/2162402X.2024.2432726","url":null,"abstract":"<p><p>Over the last decade, the annual Immunorad Conference, held under the joint auspicies of Gustave Roussy (Villejuif, France) and the Weill Cornell Medical College (New-York, USA) has aimed at exploring the latest advancements in the fields of tumor immunology and radiotherapy-immunotherapy combinations for the treatment of cancer. Gathering medical oncologists, radiation oncologists, physicians and researchers with esteemed expertise in these fields, the Immunorad Conference bridges the gap between preclinical outcomes and clinical opportunities. Thus, it paves a promising way toward optimizing radiotherapy-immunotherapy combinations and, from a broader perspective, improving therapeutic strategies for patients with cancer. Herein, we report on the topics developed by key-opinion leaders during the 7^th Immunorad Conference held in Paris-Les Cordeliers (France) from September 27th to 29th 2023, and set the stage for the 8^th edition of Immunorad which will be held at Weill Cornell Medical College (New-York, USA) in October 2024.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2432726"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856327","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":"Hyperdifferentiated murine melanoma cells promote adaptive anti-tumor immunity but activate the immune checkpoint system.","authors":"Yukie Ando, Yutaka Horiuchi, Sara Hatazawa, Momo Mataki, Akihiro Nakamura, Takashi Murakami","doi":"10.1080/2162402X.2024.2437211","DOIUrl":"10.1080/2162402X.2024.2437211","url":null,"abstract":"<p><p>Accumulating evidence suggests that phenotype switching of cancer cells is essential for therapeutic resistance. However, the immunological characteristics of drug-induced phenotype-switching melanoma cells (PSMCs) are unknown. We investigated PSMC elimination by host immunity using hyperdifferentiated melanoma model cells derived from murine B16F10 melanoma cells. Exposure of B16F10 cells to staurosporine induced a hyperdifferentiated phenotype associated with transient drug tolerance. Staurosporine-induced hyperdifferentiated B16F10 (sB16F10) cells expressed calreticulin on their surface and were phagocytosed efficiently. Furthermore, the inoculation of mice with sB16F10 cells induced immune responses against tumor-derived antigens. Despite the immunogenicity of sB16F10 cells, they activated the PD-1/PD-L1 immune checkpoint system and strongly resisted T cell-mediated tumor destruction. However, <i>in vivo</i> treatment with immune checkpoint inhibitors successfully eliminated the tumor. Thus, hyperdifferentiated melanoma cells have conflicting immunological properties - enhanced immunogenicity and immune evasion. Inhibiting the ability of PSMCs to evade T cell-mediated elimination might lead to complete melanoma eradication.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2437211"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796568","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":"An integral membrane constitutively active heparanase enhances the tumor infiltration capability of NK cells.","authors":"Liborio-Ramos Sofia, Quiros-Fernandez Isaac, Ilan Neta, Soboh Soaad, Farhoud Malik, Süleymanoglu Ruken, Bennek Michele, Calleja-Vara Sara, Müller Martin, Vlodavsky Israel, Angel Cid-Arregui","doi":"10.1080/2162402X.2024.2437917","DOIUrl":"10.1080/2162402X.2024.2437917","url":null,"abstract":"<p><p>Eradication of cancer cells by the immune system requires extravasation, infiltration and progression of immune cells through the tumor extracellular matrix (ECM). These are also critical determinants for successful adoptive cell immunotherapy of solid tumors. Together with structural proteins, such as collagens and fibronectin, heparan sulfate (HS) proteoglycans are major components of the ECM. Heparanase 1 (HPSE) is the only enzyme known to have endoglycosidase activity that degrades HS. HPSE is expressed at high levels in almost all hematopoietic cells, which suggests that it plays a relevant role in immune cell migration through solid tissues. Besides, tumor cells express also HPSE as a way to facilitate tumor cell resettlement and metastasis. Therefore, an increase in HPSE in the tumor ECM would be detrimental. Here, we analyzed the effects of constitutive expression of an active, membrane-bound HPSE on the ability of human natural killer (NK) cells to infiltrate tumors and eliminate tumor cells. We demonstrate that NK cells expressing a chimeric active form of HPSE on the cell surface as an integral membrane protein, display significantly enhanced infiltration capability into spheroids of various cancer cell lines, as well as into xenograft tumors in immunodeficient mice. As a result, tumor growth was significantly suppressed without causing noticeable side effects. Altogether, our results suggest that a constitutively expressed active HSPE on the surface of immune effector cells enhances their capability to access and eliminate tumor cells. This strategy opens new possibilities for improving adoptive immune treatments using NK cells.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2437917"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802842","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":"Assessment of adenosinergic activity of small extracellular vesicles in plasma of cancer patients and healthy donors.","authors":"Chang Sook Hong, Elizabeth V Menchikova, Yana Najjar, Theresa L Whiteside, Edwin K Jackson","doi":"10.1080/2162402X.2024.2444704","DOIUrl":"https://doi.org/10.1080/2162402X.2024.2444704","url":null,"abstract":"<p><p>The adenosinergic pathway converting endogenous ATP to adenosine (ADO) is a major immunosuppressive pathway in cancer. Emerging data indicate that plasma small extracellular vesicles (sEV) express CD39 and CD73 and produce ADO. Using a noninvasive, highly sensitive newly developed assay, metabolism of N⁶-etheno-labeled eATP, eADP or eAMP by ecto-nucleotidases on the external surface of sEV was measured using high pressure liquid chromatography with fluorescence detection. Ecto-nucleotidase activity in sEV isolated from plasma of randomly selected cancer patients and healthy donors (HDs) was compared. Relative to sEV of HDs, sEV from the plasma of melanoma patients metabolized eATP to eADP and eAMP to eADO with significantly greater efficiency. Activities of both CD39 and CD73 were elevated, as determined by the use of pharmacologic inhibitors selective for these enzymes. In contrast, metabolic activity of CD39 and CD73 on sEV isolated from plasma of patients with head and neck cancer was comparable to that of HDs, suggesting that the activity of ecto-nucleotidases on sEV may differ depending on the cancer type or cancer stage. The N⁶-etheno-purine assay measuring contributions of ecto-nucleotidases residing on the surface of sEV to the extracellular ATP to ADO pathway can discriminate cancer patients from HDs, differentiate among different cancer types, and potentially identify patients most likely to benefit from anti-adenosinergic therapy designed to inhibit the adenosine-mediated immune suppression.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2444704"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865895","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":"Clinical impact of cancer cachexia on the outcome of patients with non-small cell lung cancer with PD-L1 tumor proportion scores of ≥50% receiving pembrolizumab monotherapy versus immune checkpoint inhibitor with chemotherapy.","authors":"Hayato Kawachi, Tadaaki Yamada, Motohiro Tamiya, Yoshiki Negi, Takashi Kijima, Yasuhiro Goto, Akira Nakao, Shinsuke Shiotsu, Keiko Tanimura, Takayuki Takeda, Asuka Okada, Taishi Harada, Koji Date, Yusuke Chihara, Isao Hasegawa, Nobuyo Tamiya, Yuki Katayama, Naoya Nishioka, Kenji Morimoto, Masahiro Iwasaku, Shinsaku Tokuda, Takayuki Shimose, Koichi Takayama","doi":"10.1080/2162402X.2024.2442116","DOIUrl":"https://doi.org/10.1080/2162402X.2024.2442116","url":null,"abstract":"<p><p>This retrospective, multicenter cohort study aimed to determine whether cancer cachexia serves as a biomarker for determining the most effective treatment for patients having non-small-cell lung cancer (NSCLC) with high programmed death ligand 1 (PD-L1) expression treated with immune checkpoint inhibitors (ICIs) alone or combined with chemotherapy (ICI/chemotherapy). We included 411 patients with advanced NSCLC with a PD-L1 tumor proportion score of ≥50%. The patients were treated with pembrolizumab monotherapy or ICI/chemotherapy. Cancer cachexia was defined as a weight loss of >5% of the total body weight or a body mass index of <20 kg/m² coupled with an additional weight loss of >2% within 6 months before starting treatment. Eighty-five (21%) patients met the cancer cachexia criteria. Overall survival (OS) was significantly shorter in patients with cachexia than in those without cachexia in both the pembrolizumab monotherapy group (17.2 vs. 35.8 months, <i>p</i> < 0.001) and the ICI/chemotherapy group (27.0 months vs. not reached, <i>p</i> = 0.044). However, after stratifying by cancer cachexia status, no significant difference in OS was observed between the pembrolizumab monotherapy and chemoimmunotherapy groups, regardless of cachexia. In conclusion, ICI/chemotherapy offers limited benefits for NSCLC patients with high PD-L1 expression and concurrent cancer cachexia. Considering the frailty associated with cachexia, ICI monotherapy may be preferred to ICI/chemotherapy for these patients. New interventions that can better address the negative prognostic impact of cachexia in patients treated using ICIs with or without chemotherapy remain warranted.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2442116"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142839944","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":"Characterisation of the tumour microenvironment and PD-L1 granularity reveals the prognostic value of cancer-associated myofibroblasts in non-invasive bladder cancer.","authors":"Carmen G Cañizo, Félix Guerrero-Ramos, Mercedes Perez Escavy, Iris Lodewijk, Cristian Suárez-Cabrera, Lucía Morales, Sandra P Nunes, Ester Munera-Maravilla, Carolina Rubio, Rebeca Sánchez, Marta Rodriguez-Izquierdo, Jaime Martínez de Villarreal, Francisco X Real, Daniel Castellano, Cristina Martín-Arriscado, David Lora Pablos, Alfredo Rodríguez Antolín, Marta Dueñas, Jesús M Paramio, Victor G Martínez","doi":"10.1080/2162402X.2024.2438291","DOIUrl":"https://doi.org/10.1080/2162402X.2024.2438291","url":null,"abstract":"<p><p>High-risk non-muscle-invasive bladder cancer (NMIBC) presents high recurrence and progression rates. Despite the use of Bacillus Calmette-Guérin gold-standard immunotherapy and the recent irruption of anti-PD-1/PD-L1 drugs, we are missing a comprehensive understanding of the tumor microenvironment (TME) that may help us find biomarkers associated to treatment outcome. Here, we prospectively analyzed TME composition and PD-L1 expression of tumor and non-tumoral tissue biopsies from 73 NMIBC patients and used scRNA-seq, transcriptomic cohorts and tissue micro-array to validate the prognostic value of cell types of interest. Compared to non-tumoral tissue, NMIBC presented microvascular alterations, increased cancer-associated fibroblast (CAF) and myofibroblast (myoCAF) presence, and varied immune cell distribution, such as increased macrophage infiltration. Heterogeneous PD-L1 expression was observed across subsets, with macrophages showing the highest expression levels, but cancer cells as the primary potential anti-PD-L1 binding targets. Unbiased analysis revealed that myoCAF and M2-like macrophages are specifically enriched in high-grade NMIBC tumors. The topological distribution of these two cell types changed as NMIBC progresses, as shown by immunofluorescence. Only myoCAFs were associated with higher rates of progression and recurrence in three independent cohorts (888 total patients), reaching prediction values comparable to transcriptomic classes, which we further validated using tissue micro-array. Our study provides a roadmap to establish the landscape of the NMIBC TME, highlighting myoCAFs as potential prognostic markers.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2438291"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856324","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":"Plasma protein dynamics during ipilimumab treatment in metastatic melanoma: associations with tumor response, adverse events and survival.","authors":"Ragnhild Reehorst Lereim, Claire Dunn, Elin Aamdal, Sudhir Kumar Chauhan, Oddbjørn Straume, Tormod Kyrre Guren, Jon Amund Kyte","doi":"10.1080/2162402X.2024.2440967","DOIUrl":"https://doi.org/10.1080/2162402X.2024.2440967","url":null,"abstract":"<p><p>The immune checkpoint inhibitor ipilimumab provides long term survival in some metastatic melanoma patients, but the majority has no benefit, and may experience serious side effects. Here, we investigated the dynamics of plasma cytokine concentrations and their potential utility for predicting treatment response, adverse events and overall survival (OS) in patients with metastatic melanoma undergoing ipilimumab monotherapy. A cohort of 148 patients was examined, with plasma samples collected prior to treatment initiation and at the end of the first and second treatment cycles. Concentrations of 48 plasma proteins were measured using a multiplex immunoassay. The results revealed a general increase in cytokine levels following the first ipilimumab dose, consistent with immune activation. Patients not responding to treatment exhibited significantly elevated baseline levels of G-CSF, IL-2RA, MIP-1a, and SCF, compared to tumor responders (<i>p</i> < 0.05). Furthermore, high levels of IL-2RA, IFNγ, PDGF-bb and MIG were linked to inferior OS, while high concentrations of MIF and RANTES were associated with improved OS (<i>p</i> < 0.05). A multivariate model containing CRP, LDH, ECOG, IL-2RA and PDGF-bb identified a subgroup of patients with poor OS. Patients who experienced severe immune-related adverse events within three months of treatment initiation had higher baseline concentrations of several cytokines, indicating a potential association between preexisting inflammation and adverse events. These findings indicate that the first dose of ipilimumab induces a systemic response with increased levels of circulating cytokines and suggest candidate biomarkers for clinical response, immune-mediated toxicity and survival. Further studies in independent patient cohorts are required to confirm the findings.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2440967"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866014","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}