Oncoimmunology最新文献

{"title":"Secreted factors from M1 macrophages drive prostate cancer stem cell plasticity by upregulating NANOG, <i>SOX2</i>, and <i>CD44</i> through NFκB-signaling.","authors":"Kirsi Kainulainen, Einari A Niskanen, Johanna Kinnunen, Kaisa Mäki-Mantila, Kiia Hartikainen, Ville Paakinaho, Marjo Malinen, Kirsi Ketola, Sanna Pasonen-Seppänen","doi":"10.1080/2162402X.2024.2393442","DOIUrl":"10.1080/2162402X.2024.2393442","url":null,"abstract":"<p><p>The inflammatory tumor microenvironment (TME) is a key driver for tumor-promoting processes. Tumor-associated macrophages are one of the main immune cell types in the TME and their increased density is related to poor prognosis in prostate cancer. Here, we investigated the influence of pro-inflammatory (M1) and immunosuppressive (M2) macrophages on prostate cancer lineage plasticity. Our findings reveal that M1 macrophage secreted factors upregulate genes related to stemness while downregulating genes associated with androgen response in prostate cancer cells. The expression of cancer stem cell (CSC) plasticity markers NANOG, KLF4, <i>SOX2, OCT4</i>, and CD44 was stimulated by the secreted factors from M1 macrophages. Moreover, AR and its target gene <i>PSA</i> were observed to be suppressed in LNCaP cells treated with secreted factors from M1 macrophages. Inhibition of NFκB signaling using the IKK16 inhibitor resulted in downregulation of NANOG, <i>SOX2</i>, and <i>CD44</i> and CSC plasticity. Our study highlights that the secreted factors from M1 macrophages drive prostate cancer cell plasticity by upregulating the expression of CSC plasticity markers through NFκB signaling pathway.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2393442"},"PeriodicalIF":6.5,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034397","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":"<i>FCGR3A</i> F158V alleles frequency differs in multiple myeloma patients from healthy population.","authors":"Michaël Constantinides, Nicolas Robert, Caroline Multrier, Loïs Coënon, Mauricio Campos-Mora, Carine Jacquard, Fei Gao, Sara Zemiti, Jessy Presumey, Guillaume Cartron, Jérome Moreaux, Martin Villalba","doi":"10.1080/2162402X.2024.2388306","DOIUrl":"10.1080/2162402X.2024.2388306","url":null,"abstract":"<p><p><i>FCGR3A</i> presents a single nucleotide polymorphism at location 158 (V/F), which affects its binding to the fragment crystallizable (Fc) of antibodies (Abs). FcγRIIIa-158 V allotype has the highest affinity and is associated with a better clinical response to IgG1 monoclonal Abs (mAb) treatment. We compared the allele frequency of <i>FCGR3A-</i>F158V polymorphism in cohorts of patients with B-cell lymphoproliferative disorders, including multiple myeloma (MM), monoclonal gammopathy of undetermined significance (MGUS), non-Hodgkin lymphoma (NHL), and B-cell chronic leukemia (B-CLL). <i>FCGR3A</i>-158F homozygous were enriched and tended to be in MM and MGUS patients, respectively; but neither in B-CLL nor in NHL patients. We identified a significantly lower concentration of CD8 T-cells and resting memory CD4 T-cells in MM patients bone marrow with the F/F genotype, associated with an increase in the macrophage percentage. In contrast, natural killer cells increased in V/V homozygous patients. This suggests a deregulation of the immune microenvironment in <i>FCGR3A</i>-F/F homozygous patients. However, we did not observe difference in response following treatment combining chemotherapy associated or not with daratumumab, an IgG1 mAb direct against CD38. Our findings suggest that <i>FCGR3A</i> F158V polymorphism can regulate the immune environment and affect the development of tumor plasma cells.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2388306"},"PeriodicalIF":6.5,"publicationDate":"2024-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037402","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":"Correction.","authors":"","doi":"10.1080/2162402X.2024.2351662","DOIUrl":"https://doi.org/10.1080/2162402X.2024.2351662","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1080/2162402X.2015.1055993.].</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2351662"},"PeriodicalIF":6.5,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11321395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141977638","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":"DNA mismatch repair defect and intratumor heterogeneous deficiency differently impact immune responses in diffuse large B-cell lymphoma.","authors":"Zijun Y Xu-Monette, Cancan Luo, Li Yu, Yong Li, Govind Bhagat, Alexandar Tzankov, Carlo Visco, Xiangshan Fan, Karen Dybkaer, Ali Sakhdari, Nicholas T Wang, Alyssa F Yuan, April Chiu, Wayne Tam, Youli Zu, Eric D Hsi, Anamarija M Perry, Wenting Song, Dennis O'Malley, Qingyan Au, Harry Nunns, Heounjeong Go, Michael B Møller, Benjamin M Parsons, Santiago Montes-Moreno, Maurilio Ponzoni, Andrés J M Ferreri, Aliyah R Sohani, Jeremy S Abramson, Bing Xu, Ken H Young","doi":"10.1080/2162402X.2024.2384667","DOIUrl":"10.1080/2162402X.2024.2384667","url":null,"abstract":"<p><p>Deficient (d) DNA mismatch repair (MMR) is a biomarker predictive of better response to PD-1 blockade immunotherapy in solid tumors. dMMR can be caused by mutations in MMR genes or by protein inactivation, which can be detected by sequencing and immunohistochemistry, respectively. To investigate the role of dMMR in diffuse large B-cell lymphoma (DLBCL), MMR gene mutations and expression of MSH6, MSH2, MLH1, and PMS2 proteins were evaluated by targeted next-generation sequencing and immunohistochemistry in a large cohort of DLBCL patients treated with standard chemoimmunotherapy, and correlated with the tumor immune microenvironment characteristics quantified by fluorescent multiplex immunohistochemistry and gene-expression profiling. The results showed that genetic dMMR was infrequent in DLBCL and was significantly associated with increased cancer gene mutations and favorable immune microenvironment, but not prognostic impact. Phenotypic dMMR was also infrequent, and MMR proteins were commonly expressed in DLBCL. However, intratumor heterogeneity existed, and increased DLBCL cells with phenotypic dMMR correlated with significantly increased T cells and PD-1⁺ T cells, higher average nearest neighbor distance between T cells and PAX5⁺ cells, upregulated immune gene signatures, LE4 and LE7 ecotypes and their underlying Ecotyper-defined cell states, suggesting the possibility that increased T cells targeted only tumor cell subsets with dMMR. Only in patients with MYC¯ DLBCL, high MSH6/PMS2 expression showed significant adverse prognostic effects. This study shows the immunologic and prognostic effects of genetic/phenotypic dMMR in DLBCL, and raises a question on whether DLBCL-infiltrating PD-1⁺ T cells target only tumor subclones, relevant for the efficacy of PD-1 blockade immunotherapy in DLBCL.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2384667"},"PeriodicalIF":6.5,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11302547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141898703","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":"Selective lysis of acute myeloid leukemia cells by CD34/CD3 bispecific antibody through the activation of γδ T-cells.","authors":"Faisal Al Agrafi, Ahmed Gaballa, Paula Hahn, Lucas C M Arruda, Adrian C Jaramillo, Maartje Witsen, Sören Lehmann, Björn Önfelt, Michael Uhlin, Arwen Stikvoort","doi":"10.1080/2162402X.2024.2379063","DOIUrl":"10.1080/2162402X.2024.2379063","url":null,"abstract":"<p><p>Despite the considerable progress in acute myeloid leukemia (AML) treatment, relapse after allogeneic hematopoietic stem cell transplantation (HSCT) is still frequent and associated with a poor prognosis. Relapse has been shown to be correlated with an incomplete eradication of CD34+ leukemic stem cells prior to HSCT. Previously, we have shown that a novel CD34-directed, bispecific T-cell engager (BTE) can efficiently redirect the T-cell effector function toward cancer cells, thus eliminating leukemic cells <i>in vitro</i> and <i>in vivo</i>. However, its impact on γδ T-cells is still unclear. In this study, we tested the efficacy of the CD34-specific BTE using <i>in vitro</i> expanded γδ T-cells as effectors. We showed that the BTEs bind to γδ T-cells and CD34+ leukemic cell lines and induce target cell killing in a dose-dependent manner. Additionally, γδ T-cell mediated killing was found to be superior to αβ T-cell mediated cytotoxicity. Furthermore, we observed that only in the presence of BTE the γδ T-cells induced primary AML blast killing <i>in vitro</i>. Importantly, our results show that γδ T-cells did not target the healthy CD34^intermediate endothelial blood-brain barrier cell line (hCMEC/D3) nor lysed CD34+ HSCs from healthy bone marrow samples.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2379063"},"PeriodicalIF":6.5,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11285226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141793817","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":"Targeted opening of the blood-brain barrier facilitates doxorubicin/anti-PD-1-based chemoimmunotherapy of glioblastoma.","authors":"Jonathan G Pol, Manuela Lizarralde-Guerrero, Andrea Checcoli, Guido Kroemer","doi":"10.1080/2162402X.2024.2385124","DOIUrl":"10.1080/2162402X.2024.2385124","url":null,"abstract":"<p><p>Doxorubicin is a prototypical inducer of immunogenic cell death (ICD) that sensitizes to subsequent immunotherapy by PD-1 blockade. However, this systemic drug combination fails against glioblastoma, hidden behind the blood-brain barrier (BBB). A recent work delineates a biophysical method for BBB permeabilization that yields effective preclinical effects of chemoimmunotherapy.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2385124"},"PeriodicalIF":6.5,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11285269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141793818","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":"CXCR1/2 antagonism inhibits neutrophil function and not recruitment in cancer.","authors":"Jeff W Kwak, Helena Q Nguyen, Alex Camai, Grace M Huffman, Surapat Mekvanich, Naia N Kenney, Xiaodong Zhu, Timothy W Randolph, A McGarry Houghton","doi":"10.1080/2162402X.2024.2384674","DOIUrl":"10.1080/2162402X.2024.2384674","url":null,"abstract":"<p><p>The level of tumor and circulating CXCR1/2-expressing neutrophils and CXCR1/2 ligands correlate with poor patient outcomes, inversely correlate with tumoral lymphocyte content, and predict immune checkpoint inhibitor (ICI) treatment failure. Accordingly, CXCR2-selective and CXCR1/2 dual inhibitors exhibit activity both as single agents and in combination with ICI treatment in mouse tumor models. Based on such reports, clinical trials combining CXCR1/2 axis antagonists with ICI treatment for cancer patients are underway. It has been assumed that CXCR1/2 blockade impacts tumors by blocking neutrophil chemotaxis and reducing neutrophil content in tumors. Here, we show that while CXCR2 antagonism does slow tumor growth, it does not preclude neutrophil recruitment into tumor. Instead, CXCR1/2 inhibition alters neutrophil function by blocking the polarization of transcriptional programs toward immune suppressive phenotypes and rendering neutrophils incapable of suppressing lymphocyte proliferation. This is associated with decreased release of reactive oxygen species and Arginase-1 into the extracellular milieu. Remarkably, these therapeutics do not impact the ability of neutrophils to phagocytose and kill ingested bacteria. Taken together, these results mechanistically explain why CXCR1/2 inhibition has been active in cancer but without infectious complications.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2384674"},"PeriodicalIF":6.5,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11285219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141793816","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":"S100A10 promotes cancer metastasis via recruitment of MDSCs within the lungs.","authors":"Juan Li, Can Zhou, Xiaoqian Gao, Tan Tan, Miao Zhang, Yazhao Li, He Chen, Ruiqi Wang, Bo Wang, Jie Liu, Peijun Liu","doi":"10.1080/2162402X.2024.2381803","DOIUrl":"10.1080/2162402X.2024.2381803","url":null,"abstract":"<p><p>Tumor-derived exosomes bind to organ resident cells, activating S100 molecules during the remodeling of the local immune microenvironment. However, little is known regarding how organ resident cell S100A10 mediates cancer metastatic progression. Here, we provided evidence that S100A10 plays an important role in regulating the lung immune microenvironment and cancer metastasis. S100A10-deficient mice reduced cancer metastasis in the lung. Furthermore, the activation of S100A10 within lung fibroblasts via tumor-derived exosomes increased the expression of CXCL1 and CXCL8 chemokines, accompanied by the myeloid-derived suppressor cells (MDSCs) recruitment. S100A10 inhibitors such as 1-Substituted-4-Aroyl-3-hydroxy-5-Phenyl-1 H-5-pyrrol-2(5 H)-ones inhibit lung metastasis in vivo. Our findings highlight the crucial role of S100A10 in driving MDSC recruitment in order to remodel the lung immune microenvironment and provide potential therapeutic targets to block cancer metastasis to the lung.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2381803"},"PeriodicalIF":6.5,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11275524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141790888","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":"In-depth analysis of the interplay between oncogenic mutations and NK cell-mediated cancer surveillance in solid tumors.","authors":"Cecilia Pesini, Laura Artal, Jorge Paúl Bernal, Diego Sánchez Martinez, Julián Pardo, Ariel Ramírez-Labrada","doi":"10.1080/2162402X.2024.2379062","DOIUrl":"10.1080/2162402X.2024.2379062","url":null,"abstract":"<p><p>Natural killer (NK) cells play a crucial role in antitumoral and antiviral responses. Yet, cancer cells can alter themselves or the microenvironment through the secretion of cytokines or other factors, hindering NK cell activation and promoting a less cytotoxic phenotype. These resistance mechanisms, often referred to as the \"hallmarks of cancer\" are significantly influenced by the activation of oncogenes, impacting most, if not all, of the described hallmarks. Along with oncogenes, other types of genes, the tumor suppressor genes are frequently mutated or modified during cancer. Traditionally, these genes have been associated with uncontrollable tumor growth and apoptosis resistance. Recent evidence suggests oncogenic mutations extend beyond modulating cell death/proliferation programs, influencing cancer immunosurveillance. While T cells have been more studied, the results obtained highlight NK cells as emerging key protagonists for enhancing tumor cell elimination by modulating oncogenic activity. A few recent studies highlight the crucial role of oncogenic mutations in NK cell-mediated cancer recognition, impacting angiogenesis, stress ligands, and signaling balance within the tumor microenvironment. This review will critically examine recent discoveries correlating oncogenic mutations to NK cell-mediated cancer immunosurveillance, a relatively underexplored area, particularly in the era dominated by immune checkpoint inhibitors and CAR-T cells. Building on these insights, we will explore opportunities to improve NK cell-based immunotherapies, which are increasingly recognized as promising alternatives for treating low-antigenic tumors, offering significant advantages in terms of safety and manufacturing suitability.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2379062"},"PeriodicalIF":6.5,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11259085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735429","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 NK cells and cancer.","authors":"Claudia Cantoni, Michela Falco, Massimo Vitale, Gabriella Pietra, Enrico Munari, Daniela Pende, Maria Cristina Mingari, Simona Sivori, Lorenzo Moretta","doi":"10.1080/2162402X.2024.2378520","DOIUrl":"10.1080/2162402X.2024.2378520","url":null,"abstract":"<p><p>The long story of NK cells started about 50 y ago with the first demonstration of a natural cytotoxic activity within an undefined subset of circulating leukocytes, has involved an ever-growing number of researchers, fascinated by the apparently easy-to-reach aim of getting a \"universal anti-tumor immune tool\". In fact, in spite of the impressive progress obtained in the first decades, these cells proved far more complex than expected and, paradoxically, the accumulating findings have continuously moved forward the attainment of a complete control of their function for immunotherapy. The refined studies of these latter years have indicated that NK cells can epigenetically calibrate their functional potential, in response to specific environmental contexts, giving rise to extraordinarily variegated subpopulations, comprehensive of memory-like cells, tissue-resident cells, or cells in various differentiation stages, or distinct functional states. In addition, NK cells can adapt their activity in response to a complex body of signals, spanning from the interaction with either suppressive or stimulating cells (myeloid-derived suppressor cells or dendritic cells, respectively) to the engagement of various receptors (specific for immune checkpoints, cytokines, tumor/viral ligands, or mediating antibody-dependent cell-mediated cytotoxicity). According to this picture, the idea of an easy and generalized exploitation of NK cells is changing, and the way is opening toward new carefully designed, combined and personalized therapeutic strategies, also based on the use of genetically modified NK cells and stimuli capable of strengthening and redirecting their effector functions against cancer.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2378520"},"PeriodicalIF":6.5,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11253890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141635065","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}