Oncoimmunology最新文献

{"title":"Identification of RNA-binding protein hnRNP C targeting the 3'UTR of the TAP-associated glycoprotein tapasin in melanoma.","authors":"Yuan Wang, Barbara Seliger","doi":"10.1080/2162402X.2024.2370928","DOIUrl":"10.1080/2162402X.2024.2370928","url":null,"abstract":"<p><p>Deregulation or loss of the human leukocyte antigen class I (HLA-I) molecules on tumor cells leading to inhibition of CD8⁺ T cell recognition is an important tumor immune escape strategy, which could be caused by a posttranscriptional control of molecules in the HLA-I pathway mediated by RNA-binding proteins (RBPs). So far, there exists only limited information about the interaction of RBPs with HLA-I-associated molecules, but own work demonstrated a binding of the heterogeneous ribonucleoprotein C (hnRNP C) to the 3' untranslated region (UTR) of the TAP-associated glycoprotein tapasin (tpn). In this study, <i>in silico</i> analysis of pan-cancer TCGA datasets revealed that hnRNP C is higher expressed in tumor specimens compared to corresponding normal tissues, which is negatively correlated to tpn expression, T cell infiltration and the overall survival of tumor patients. Functional analysis demonstrated an upregulation of tpn expression upon siRNA-mediated downregulation of hnRNP C, which is accompanied by an increased HLA-I surface expression. Thus, hnRNP C has been identified to target tpn and its inhibition could improve the HLA-I surface expression on melanoma cells suggesting its use as a possible biomarker for T-cell-based tumor immunotherapies.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2370928"},"PeriodicalIF":6.5,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11212565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471771","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":"Modulation of blood T cell polyfunctionality and HVEM/BTLA expression are critical determinants of clinical outcome in anti-PD1-treated metastatic melanoma patients.","authors":"Stéphane Dalle, Estelle Verronese, Axelle N'Kodia, Christine Bardin, Céline Rodriguez, Thibault Andrieu, Anais Eberhardt, Gabriel Chemin, Uzma Hasan, Myrtille Le-Bouar, Julie Caramel, Mona Amini-Adle, Nathalie Bendriss-Vermare, Bertrand Dubois, Christophe Caux, Christine Ménétrier-Caux","doi":"10.1080/2162402X.2024.2372118","DOIUrl":"10.1080/2162402X.2024.2372118","url":null,"abstract":"<p><p>The need for reliable biomarkers to predict clinical benefit from anti-PD1 treatment in metastatic melanoma (MM) patients remains unmet. Several parameters have been considered in the tumor environment or the blood, but none has yet achieved sufficient accuracy for routine clinical practice. Whole blood samples from MM patients receiving second-line anti-PD1 treatment (NCT02626065), collected longitudinally, were analyzed by flow cytometry to assess the immune cell subsets absolute numbers, the expression of immune checkpoints or ligands on T cells and the functionality of innate immune cells and T cells. Clinical response was assessed according to Progression-Free Survival (PFS) status at one-year following initiation of anti-PD1 (responders: PFS > 1 year; non-responders: PFS ≤ 1 year). At baseline, several phenotypic and functional alterations in blood immune cells were observed in MM patients compared to healthy donors, but only the proportion of polyfunctional memory CD4+ T cells was associated with response to anti-PD1. Under treatment, a decreased frequency of HVEM on CD4+ and CD8+ T cells after 3 months of treatment identified responding patients, whereas its receptor BTLA was not modulated. Both reduced proportion of CD69-expressing CD4+ and CD8+ T cells and increased number of polyfunctional blood memory T cells after 3 months of treatment were associated with response to anti-PD1. Of upmost importance, the combination of changes of all these markers accurately discriminated between responding and non-responding patients. These results suggest that drugs targeting HVEM/BTLA pathway may be of interest to improve anti-PD1 efficacy.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2372118"},"PeriodicalIF":6.5,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11210932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471772","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 study of spartalizumab (PDR001) among patients with recurrent or metastatic esophageal squamous cell carcinoma (KCSG HN18-17, K-MASTER project 12).","authors":"Dong Ki Lee, Sook Ryun Park, Yeul Hong Kim, Yun-Gyoo Lee, Su-Jin Shin, Beung-Chul Ahn, Sung Sook Lee, Sun Min Lim, Hye Ryun Kim, Byoung Chul Cho, Min Hee Hong","doi":"10.1080/2162402X.2024.2371563","DOIUrl":"10.1080/2162402X.2024.2371563","url":null,"abstract":"<p><p>Spartalizumab (PDR001) is a humanized IgG4 monoclonal antibody targeting programmed cell death protein 1 (PD-1). We conducted a single-arm, phase 2 trial to investigate the efficacy and safety of spartalizumab in patients with refractory esophageal squamous cell carcinoma (ESCC). Patients with histologically confirmed ESCC who experienced disease progression after platinum-based chemotherapy received 300 mg of intravenous spartalizumab every three weeks until disease progression or occurrence of unacceptable toxicity. The primary endpoint was centrally assessed objective response according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Adverse events were closely monitored throughout the study. From March 2020 through April 2021, 44 patients with ESCC were enrolled. Of the 44 patients, the objective response rate was 20.5% (95% confidence interval: 8.5-32.4). With a median follow-up of 10.9 months, median progression-free survival and overall survival were 3.2 months and 11.2 months, respectively. In addition, the median duration of response was 24.7 months. The most common grade 3 or 4 adverse event was grade 3 dysphagia (eight [18%] patients). Biomarker analyses explored programmed cell death ligand 1 and CD20 as potential predictive markers for PD-1 blockade. Spartalizumab showed promising activity with a manageable safety profile, indicating its potential as a new treatment option for patients with refractory ESCC.</p><p><strong>Trial registration: </strong>The trial was registered at ClinicalTrials.gov under the identifier NCT03785496.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2371563"},"PeriodicalIF":6.5,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11197908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141451984","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 β2-integrin function results in metabolic reprogramming of dendritic cells, leading to increased dendritic cell functionality and anti-tumor responses.","authors":"Heidi Harjunpää, Riku Somermäki, Guillem Saldo Rubio, Manlio Fusciello, Sara Feola, Imrul Faisal, Anni I Nieminen, Liang Wang, Marc Llort Asens, Hongxia Zhao, Ove Eriksson, Vincenzo Cerullo, Susanna C Fagerholm","doi":"10.1080/2162402X.2024.2369373","DOIUrl":"10.1080/2162402X.2024.2369373","url":null,"abstract":"<p><p>Dendritic cells (DCs) are the main antigen presenting cells of the immune system and are essential for anti-tumor responses. DC-based immunotherapies are used in cancer treatment, but their functionality is not optimized and their clinical efficacy is currently limited. Approaches to improve DC functionality in anti-tumor immunity are therefore required. We have previously shown that the loss of β2-integrin-mediated adhesion leads to epigenetic reprogramming of bone marrow-derived DCs (BM-DCs), resulting in an increased expression of costimulatory markers (CD86, CD80, and CD40), cytokines (IL-12) and the chemokine receptor CCR7. We now show that the loss of β2-integrin-mediated adhesion of BM-DCs also leads to a generally suppressed metabolic profile, with reduced metabolic rate, decreased ROS production, and lowered glucose uptake in cells. The mRNA levels of glycolytic enzymes and glucose transporters were reduced, indicating transcriptional regulation of the metabolic phenotype. Surprisingly, although signaling through a central regulator of immune cell metabolisms, the mechanistic target of rapamycin (mTOR), was increased in BM-DCs with dysfunctional integrins, rapamycin treatment revealed that mTOR signaling was not involved in suppressing DC metabolism. Instead, bioinformatics and functional analyses showed that the Ikaros transcription factor may be involved in regulating the metabolic profile of non-adhesive DCs. Inversely, we found that induction of metabolic stress through treatment of cells with low levels of an inhibitor of glycolysis, 2-deoxyglucose (2DG), led to increased BM-DC activation. Specifically, 2DG treatment led to increased levels of <i>Il-12</i> and <i>Ccr7</i> mRNA, increased production of IL-12, increased levels of cell surface CCR7 and increased <i>in vitro</i> migration and T cell activation potential. Furthermore, 2DG treatment led to increased histone methylation in cells (H3K4me3, H3K27me3), indicating metabolic reprogramming. Finally, metabolic stress induced by 2DG treatment led to improved BM-DC-mediated anti-tumor responses <i>in vivo</i> in a melanoma cancer model, B16-OVA. In conclusion, our results indicate a role for β2-integrin-mediated adhesion in regulating a novel type of metabolic reprogramming of DCs and DC-mediated anti-tumor responses, which may be targeted to enhance DC-mediated anti-tumor responses in cancer immunotherapy.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2369373"},"PeriodicalIF":6.5,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11195491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141447327","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":"ADA/CD26 axis increases intra-tumor PD-1⁺CD28⁺CD8⁺ T-cell fitness and affects NSCLC prognosis and response to ICB.","authors":"Ornella Franzese, Belinda Palermo, Giuseppe Frisullo, Mariangela Panetta, Giulia Campo, Daniel D'Andrea, Isabella Sperduti, Riccardo Taje, Paolo Visca, Paola Nisticò","doi":"10.1080/2162402X.2024.2371051","DOIUrl":"10.1080/2162402X.2024.2371051","url":null,"abstract":"<p><p>Improving cancer immunotherapy efficacy hinges on identifying key T-cell populations critical for tumor control and response to Immune Checkpoint Blockade (ICB). We have recently reported that while the co-expression of PD-1 and CD28 is associated with impaired functionality in peripheral blood, it significantly enhances T-cell fitness in the tumor site of non-small cell lung cancer (NSCLC) patients. To uncover the underlying mechanisms, we explored the role of CD26, a key player in T-cell activation through its interaction with adenosine deaminase (ADA), a crucial intra/extracellular enzyme able to neutralize local adenosine (ADO). We found that an autocrine ADA/CD26 axis enhances CD8⁺PD-1⁺CD28⁺ T-cell function, particularly within an immunosuppressive environment marked by CD39 expression. Then, we interrogated the TCGA and OAK datasets to gain insight into the prognostic/predictive potential of our findings. We identified a signature predicting overall survival (OS) in LUAD patients and response to atezolizumab in advanced LUAD cases. These findings suggest promising avenues for therapeutic intervention targeting the ADA/CD26 axis.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2371051"},"PeriodicalIF":6.5,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11195478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141447326","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":"Near-infrared duocarmycin photorelease from a Treg-targeted antibody-drug conjugate improves efficacy of PD-1 blockade in syngeneic murine tumor models.","authors":"Hiroshi Fukushima, Aki Furusawa, Seiichiro Takao, Ebaston Thankarajan, Michael P Luciano, Syed Muhammad Usama, Makoto Kano, Shuhei Okuyama, Hiroshi Yamamoto, Motofumi Suzuki, Miyu Kano, Peter L Choyke, Martin J Schnermann, Hisataka Kobayashi","doi":"10.1080/2162402X.2024.2370544","DOIUrl":"10.1080/2162402X.2024.2370544","url":null,"abstract":"<p><p>Regulatory T cells (Tregs) play a crucial role in mediating immunosuppression in the tumor microenvironment. Furthermore, Tregs contribute to the lack of efficacy and hyperprogressive disease upon Programmed cell death protein 1 (PD-1) blockade immunotherapy. Thus, Tregs are considered a promising therapeutic target, especially when combined with PD-1 blockade. However, systemic depletion of Tregs causes severe autoimmune adverse events, which poses a serious challenge to Treg-directed therapy. Here, we developed a novel treatment to locally and predominantly damage Tregs by near-infrared duocarmycin photorelease (NIR-DPR). In this technology, we prepared anti-CD25 F(ab')₂ conjugates, which site-specifically uncage duocarmycin in CD25-expressing cells upon exposure to NIR light. <i>In vitro</i>, CD25-targeted NIR-DPR significantly increased apoptosis of CD25-expressing HT2-A5E cells. When tumors were irradiated with NIR light <i>in vivo</i>, intratumoral CD25⁺ Treg populations decreased and Ki-67 and Interleukin-10 expression was suppressed, indicating impaired functioning of intratumoral CD25⁺ Tregs. CD25-targeted NIR-DPR suppressed tumor growth and improved survival in syngeneic murine tumor models. Of note, CD25-targeted NIR-DPR synergistically enhanced the efficacy of PD-1 blockade, especially in tumors with higher CD8⁺/Treg PD-1 ratios. Furthermore, the combination therapy induced significant anti-cancer immunity including maturation of dendritic cells, extensive intratumoral infiltration of cytotoxic CD8⁺ T cells, and increased differentiation into CD8⁺ memory T cells. Altogether, CD25-targeted NIR-DPR locally and predominantly targets Tregs in the tumor microenvironment and synergistically improves the efficacy of PD-1 blockade, suggesting that this combination therapy can be a rational anti-cancer combination immunotherapy.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2370544"},"PeriodicalIF":6.5,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11195482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141447328","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":"CD28-CD57+ T cells from head and neck cancer patients produce high levels of cytotoxic granules and type II interferon but are not senescent.","authors":"Brendan L C Kinney, Brianna Brammer, Vikash Kansal, Connor J Parrish, Haydn T Kissick, Yuan Liu, Nabil F Saba, Zachary S Buchwald, Mark W El-Deiry, Mihir R Patel, Brian J Boyce, Azeem S Kaka, Jennifer H Gross, H Michael Baddour, Amy Y Chen, Nicole C Schmitt","doi":"10.1080/2162402X.2024.2367777","DOIUrl":"10.1080/2162402X.2024.2367777","url":null,"abstract":"<p><p>T lymphocytes expressing CD57 and lacking costimulatory receptors CD27/CD28 have been reported to accumulate with aging, chronic infection, and cancer. These cells are described as senescent, with inability to proliferate but enhanced cytolytic and cytokine-producing capacity. However, robust functional studies on these cells taken directly from cancer patients are lacking. We isolated these T cells and their CD27/28+ counterparts from blood and tumor samples of 50 patients with previously untreated head and neck cancer. Functional studies confirmed that these cells have enhanced ability to degranulate and produce IFN-γ. They also retain the ability to proliferate, thus are not senescent. These data suggest that CD27/28-CD57+ CD8+ T cells are a subset of highly differentiated, CD45RA+ effector memory (T_EMRA) cells with retained proliferative capacity. Patients with > 34% of these cells among CD8+ T cells in the blood had a higher rate of locoregional disease relapse, suggesting these cells may have prognostic significance.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2367777"},"PeriodicalIF":6.5,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11181932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421500","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":"Improving STING agonist-based cancer therapy by inhibiting the autophagy-related protein VPS34.","authors":"Elisabetta Bartolini, Kris Van Moer, Bassam Janji","doi":"10.1080/2162402X.2024.2364958","DOIUrl":"10.1080/2162402X.2024.2364958","url":null,"abstract":"<p><p>We have recently demonstrated that inhibiting VPS34 enhances T-cell-recruiting chemokines through the activation of the cGAS/STING pathway using the STING agonist ADU-S100. Combining VPS34 inhibitors with ADU-S100 increased cytokine release and improved tumor control in mouse models, suggesting a potential synergy between VPS34 inhibition and therapies based on STING agonists.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2364958"},"PeriodicalIF":6.5,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11174119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141318661","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":"Exploring immune status in peripheral blood and tumor tissue in association with survival in patients with multi-organ metastatic colorectal cancer.","authors":"Lotte Bakkerus, Beatriz Subtil, Hetty J Bontkes, Elske C Gootjes, Martine Reijm, Manon Vullings, Kiek Verrijp, John-Melle Bokhorst, Carmen Woortman, Iris D Nagtegaal, Marianne A Jonker, Hans J van der Vliet, Cornelis Verhoef, Mark A J Gorris, I Jolanda M de Vries, Tanja D de Gruijl, Henk M W Verheul, Tineke E Buffart, Daniele V F Tauriello","doi":"10.1080/2162402X.2024.2361971","DOIUrl":"10.1080/2162402X.2024.2361971","url":null,"abstract":"<p><p>Colorectal cancer (CRC) raises considerable clinical challenges, including a high mortality rate once the tumor spreads to distant sites. At this advanced stage, more accurate prediction of prognosis and treatment outcome is urgently needed. The role of cancer immunity in metastatic CRC (mCRC) is poorly understood. Here, we explore cellular immune cell status in patients with multi-organ mCRC. We analyzed T cell infiltration in primary tumor sections, surveyed the lymphocytic landscape of liver metastases, and assessed circulating mononuclear immune cells. Besides asking whether immune cells are associated with survival at this stage of the disease, we investigated correlations between the different tissue types; as this could indicate a dominant immune phenotype. Taken together, our analyses corroborate previous observations that higher levels of CD8+ T lymphocytes link to better survival outcomes. Our findings therefore extend evidence from earlier stages of CRC to indicate an important role for cancer immunity in disease control even after metastatic spreading to multiple organs. This finding may help to improve predicting outcome of patients with mCRC and suggests a future role for immunotherapeutic strategies.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2361971"},"PeriodicalIF":7.2,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11168219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141312070","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":"HUNK as a key regulator of tumor-associated macrophages in triple negative breast cancer.","authors":"Nicole Ramos Solis, Anthony Cannon, Tinslee Dilday, Melissa Abt, Adrian L Oblak, Adam C Soloff, Mark H Kaplan, Elizabeth S Yeh","doi":"10.1080/2162402X.2024.2364382","DOIUrl":"10.1080/2162402X.2024.2364382","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) lacks the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). TNBC tumors are not sensitive to endocrine therapy, and standardized TNBC treatment regimens are lacking. TNBC is a more immunogenic subtype of breast cancer, making it more responsive to immunotherapy intervention. Tumor-associated macrophages (TAMs) constitute one of the most abundant immune cell populations in TNBC tumors and contribute to cancer metastasis. This study examines the role of the protein kinase HUNK in tumor immunity. Gene expression analysis using NanoString's nCounter PanCancer Immune Profiling panel identified that targeting HUNK is associated with changes in the IL-4/IL-4 R cytokine signaling pathway. Experimental analysis shows that HUNK kinase activity regulates IL-4 production in mammary tumor cells, and this regulation is dependent on STAT3. In addition, HUNK-dependent regulation of IL-4 secreted from tumor cells induces polarization of macrophages into an M2-like phenotype associated with TAMs. In return, IL-4 induces cancer metastasis and macrophages to produce epidermal growth factor. These findings delineate a paracrine signaling exchange between tumor cells and TAMs regulated by HUNK and dependent on IL-4/IL-4 R. This highlights the potential of HUNK as a target for reducing TNBC metastasis through modulation of the TAM population.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2364382"},"PeriodicalIF":6.5,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11155704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141285048","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}