Oncoimmunology最新文献

{"title":"Markers of tumor-associated macrophages and microglia exhibit high intratumoral heterogeneity in human glioblastoma tissue.","authors":"Mikael Ispirjan, Sascha Marx, Eric Freund, Steffen K Fleck, Joerg Baldauf, Karl Roessler, Henry W S Schroeder, Sander Bekeschus","doi":"10.1080/2162402X.2024.2425124","DOIUrl":"10.1080/2162402X.2024.2425124","url":null,"abstract":"<p><strong>Background: </strong>Human glioblastoma multiforme (GBM) is a highly aggressive tumor with insufficient therapies available. Especially, novel concepts of immune therapies fail due to a complex immunosuppressive microenvironment, high mutational rates, and inter-patient variations. The intratumoral heterogeneity is currently not sufficiently investigated.</p><p><strong>Methods: </strong>Biopsies from six different locations were taken in a cohort of 16 GBM patients who underwent surgery. The tissue slides were analyzed utilizing high-content imaging microscopy and algorithm-based image quantification. Several immune markers for macrophage and microglia subpopulations were investigated. Flow cytometry was used to validate key results. Besides the surface marker, cytokines were measured and categorized based on their heterogenicity and overall expression.</p><p><strong>Results: </strong>M2-like antigens, including CD204, CD163, Arg1, and CSF1R, showed comparatively higher expression, with GFAP displaying the least intratumoral heterogeneity. In contrast, anti-tumor-macrophage-like antigens, such as PSGL-1, CD16, CD68, and MHC-II, exhibited low overall expression and concurrent high intratumoral heterogeneity. CD16 and PSGL-1 were the most heterogeneous antigens. High expression levels were observed for cytokines IL-6, VEGF, and CCL-2. VILIP-a was revealed to differentiate most in principle component analysis. Cytokines with the lowest overall expression, such as TGF-β1, β-NGF, TNF-α, and TREM1, showed low intratumoral heterogeneity, in contrast to βNGF, TNF-α, and IL-18, which displayed high heterogeneity despite low expression.</p><p><strong>Conclusion: </strong>The study showed high intratumoral heterogeneity in GBM, emphasizing the need for a more detailed understanding of the tumor microenvironment. The described findings could be essential for future personalized treatment strategies and the implementation of reliable diagnostics in GBM.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2425124"},"PeriodicalIF":6.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11556281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142630958","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":"Systemic administration of a viral nanoparticle neoadjuvant prevents lung metastasis development through emergency myelopoiesis.","authors":"Léa Bourguignon, Roxann Hétu-Arbour, Tania Charpentier, Marilène Bolduc, Denis Leclerc, Krista M Heinonen, Alain Lamarre","doi":"10.1080/2162402X.2024.2429846","DOIUrl":"https://doi.org/10.1080/2162402X.2024.2429846","url":null,"abstract":"<p><p>Cancer presents a significant public health concern, particularly in the context of metastatic disease. Surgical removal of primary tumors, while essential, can inadvertently heighten the risk of metastasis. Thus, there is a critical need for innovative neoadjuvant therapies capable of curtailing metastatic progression before or immediately following tumor resection. Addressing this imperative, the papaya mosaic virus nanoparticle (PapMV) has demonstrated potent immunostimulatory capabilities against both viruses and tumors, effectively hindering their proliferation. Our study reveals that PapMV exerts a protective effect against lung metastasis when administered systemically prior to tumor implantation or during the early stages of metastasis in various mouse models of cancer. This anti-tumor effect is initiated by the recruitment of myeloid cells in the lungs. These cells adopt a pro-inflammatory profile, secreting cytokines such as IFN-α, thus fostering a tumor microenvironment inhospitable to tumor progression. Crucially, this protective mechanism hinges on the presence of macrophages before treatment. TLR7 and IFN-I signaling pathways also play pivotal roles in this process. Furthermore, our findings demonstrate that PapMV triggers the activation of the bone marrow emergency response, which accounts for the influx of myeloid cells into the lungs. This study unveils a novel aspect of PapMV's functionality. By bolstering the immune system, PapMV confers robust protection against metastasis at an early stage of disease progression. This discovery holds promise for therapeutic intervention, particularly as a preemptive measure prior to or just after surgical intervention.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2429846"},"PeriodicalIF":6.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649383","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":"Estrogen-related differences in antitumor immunity and gut microbiome contribute to sexual dimorphism of colorectal cancer.","authors":"Georgia Lattanzi, Federica Perillo, Angélica Díaz-Basabe, Bruna Caridi, Chiara Amoroso, Alberto Baeri, Elisa Cirrincione, Michele Ghidini, Barbara Galassi, Elisa Cassinotti, Ludovica Baldari, Luigi Boni, Maurizio Vecchi, Flavio Caprioli, Federica Facciotti, Francesco Strati","doi":"10.1080/2162402X.2024.2425125","DOIUrl":"10.1080/2162402X.2024.2425125","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is a multifaceted disease whose development and progression varies depending on tumor location, age of patients, infiltration of immune cells within cancer lesions, and the tumor microenvironment. These pathophysiological characteristics are additionally influenced by sex-related differences. The gut microbiome plays a role in initiation and progression of CRC, and shapes anti-tumor immune responses but how responsiveness of the immune system to the intestinal microbiota may contribute to sexual dimorphism of CRC is largely unknown. We studied survival, tumor-infiltrating immune cell populations and tumor-associated microbiome of a cohort of <i>n</i> = 184 male and female CRC patients through high-dimensional single-cell flow cytometry and 16S rRNA gene sequencing. We functionally tested the immune system-microbiome interactions in in-vivo and in-vitro models of the disease. High-dimensional single-cell flow cytometry showed that female patients are enriched by tumor-infiltrating invariant Natural Killer T (iNKT) cells but depleted by cytotoxic T lymphocytes. The enrichment of oral pathobionts and a reduction of β-glucuronidase activity are distinctive traits characterizing the gut microbiome of female patients affected by CRC. Functional assays using a collection of human primary iNKT cell lines demonstrated that the gut microbiota of female patients functionally impairs iNKT cell anti-tumor functions interfering with the granzyme-perforin cytotoxic pathway. Our results highlight a sex-dependent functional relationship between the gut microbiome, estrogen metabolism, and the decline of cytotoxic T cell responses, contributing to the sexual dimorphism observed in CRC patients with relevant implications for precision medicine and the design of targeted therapeutic approaches addressing sex bias in cancer.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2425125"},"PeriodicalIF":6.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11572150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644638","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":"FGL2_172-220 peptides improve the antitumor effect of HCMV-IE1mut vaccine against glioblastoma by modulating immunosuppressive cells in the tumor microenvironment.","authors":"Shan Wang, Shasha Jiang, Xu Li, Huan Huang, Xu Qiu, Meng Yu, Xiaoli Yang, Fengjun Liu, Chen Wang, Wen Shen, Yunyang Wang, Bin Wang","doi":"10.1080/2162402X.2024.2423983","DOIUrl":"10.1080/2162402X.2024.2423983","url":null,"abstract":"<p><p>Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor characterized by poor prognosis and lack of effective treatments. In recent years, peptide vaccines that use sequences based on tumor-specific or tumor-associated antigens to activate immune responses against tumor cells have emerged as a new therapeutic strategy. In this study, we developed a novel therapeutic polypeptide vaccine targeting the tumor-associated antigen Fibrinogen-Like Protein 2 (FGL2), whose dominant epitope peptide was tandemly linked to the C-terminus of HCMV-IE1mut via a linker. We used this vaccine to compare the therapeutic efficacy of HCMV-IE1mut alone versus HCMV-IE1mut-FGL2_172-220 and investigate the potential mechanism of action of HCMV-IE1mut-FGL2_172-220 in glioma treatment. An in situ GBM model (GL261-IE1-luc cells) was used to determine the efficacy of the vaccine. Treatment with HCMV-IE1mut-FGL2_172-220 exerted antitumor effects and extended the survival of the GL261 animal model. We observed reduced proportions of microglia, regulatory T cells (Treg), and myeloid-derived suppressor cells (MDSC) in the tumor microenvironment (TME) by immunofluorescence. Flow cytometry showed that compared to HCMV-IE1mut alone, treatment with HCMV-IE1mut-FGL2_172-220 increased the proportion of CD8+ T cells and tissue-resident memory T cells (TRM). ELISA analysis showed that it improved the secretion of tumor-specific IFN-γ and TNF-α by these cells and downregulated the expression of IL-6 and IL-10. Our study demonstrates that the long-peptide FGL2_172-220 improves the antitumor efficacy of HCMV-IE1mut, possibly by reshaping immune cells in the glioma microenvironment. These findings lay the groundwork for the development of therapeutic antigenic peptide vaccines to improve antitumor effects for cancer.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2423983"},"PeriodicalIF":5.3,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607002","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":"HLA class II neoantigen presentation for CD4⁺ T cell surveillance in HLA class II-negative colorectal cancer.","authors":"Satoru Matsumoto, Takahiro Tsujikawa, Serina Tokita, Mai Mohamed Bedeir, Kazuhiko Matsuo, Fumitake Hata, Yoshihiko Hirohashi, Takayuki Kanaseki, Toshihiko Torigoe","doi":"10.1080/2162402X.2024.2404665","DOIUrl":"10.1080/2162402X.2024.2404665","url":null,"abstract":"<p><p>Neoantigen-reactive CD4⁺ T cells play a key role in the anti-tumor immune response. However, the majority of epithelial tumors are negative for HLA class II (HLA-II) surface expression, and less is known about the processing of HLA-II antigens. Here, we directly identified naturally presented HLA-II neoantigens in HLA-II negative colorectal cancer (CRC) tissue using a proteogenomic approach. The neoantigens were immunogenic and induced patient CD4⁺ T cells with a Th1-like memory phenotype that produced IFN-γ, IL2 and TNF-α. Multiplex immunohistochemistry (IHC) demonstrated an interaction between Th cells and HLA-II-positive antigen-presenting cells (APCs) at the invasive margin and within the tertiary lymphoid structures (TLS). In our CRC cohort, the density of stromal APCs was associated with HLA-II antigen presentation in the tumor microenvironment (TME), and the number of TLS was positively correlated with the number of somatic mutations in the tumors. These results demonstrate the presence of neoantigen-specific CD4⁺ surveillance in HLA-II-negative CRC and suggest a potential role for macrophages and dendritic cells (DCs) at the invasive margin and in TLS for antigen presentation. Stromal APCs in the TME can potentially be used as a source for HLA-II neoantigen identification.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2404665"},"PeriodicalIF":5.3,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607005","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":"Immunogenic cell death inducers and PD-1 blockade as neoadjuvant therapy for rectal cancer.","authors":"Yan Wang, Liwei Zhao, Zhen Zhang, Peng Liu","doi":"10.1080/2162402X.2024.2416558","DOIUrl":"10.1080/2162402X.2024.2416558","url":null,"abstract":"<p><p>Immuno-oncological cancer management is shifting to neoadjuvant treatments. In patients with gastrointestinal cancers, particularly locally advanced rectal cancer, neoadjuvant chemoimmunotherapy often induce complete responses, hence avoiding surgical intervention. Recent clinical trials indicate that combinations of oxaliplatin-based chemotherapy and PD-1/PD-L1-targeting immunotherapy can be safely administered before surgery with curative intent.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2416558"},"PeriodicalIF":6.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478268","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":"Trial watch: anticancer vaccination with dendritic cells.","authors":"Francisca Borges, Raquel S Laureano, Isaure Vanmeerbeek, Jenny Sprooten, Octavie Demeulenaere, Jannes Govaerts, Lisa Kinget, Saurabh Saraswat, Benoit Beuselinck, Steven De Vleeschouwer, Paul Clement, Frederik De Smet, Rüdiger V Sorg, Angeliki Datsi, Nathalie Vigneron, Stefan Naulaerts, Abhishek D Garg","doi":"10.1080/2162402X.2024.2412876","DOIUrl":"https://doi.org/10.1080/2162402X.2024.2412876","url":null,"abstract":"<p><p>Dendritic cells (DCs) are critical players at the intersection of innate and adaptive immunity, making them ideal candidates for anticancer vaccine development. DC-based immunotherapies typically involve isolating patient-derived DCs, pulsing them with tumor-associated antigens (TAAs) or tumor-specific antigens (TSAs), and utilizing maturation cocktails to ensure their effective activation. These matured DCs are then reinfused to elicit tumor-specific T-cell responses. While this approach has demonstrated the ability to generate potent immune responses, its clinical efficacy has been limited due to the immunosuppressive tumor microenvironment. Recent efforts have focused on enhancing the immunogenicity of DC-based vaccines, particularly through combination therapies with T cell-targeting immunotherapies. This Trial Watch summarizes recent advances in DC-based cancer treatments, including the development of new preclinical and clinical strategies, and discusses the future potential of DC-based vaccines in the evolving landscape of immuno-oncology.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2412876"},"PeriodicalIF":6.5,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11469433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478270","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 landscape of T-cell engagers for the treatment of follicular lymphoma.","authors":"Alfredo Rivas-Delgado, Ivan Landego, Lorenzo Falchi","doi":"10.1080/2162402X.2024.2412869","DOIUrl":"https://doi.org/10.1080/2162402X.2024.2412869","url":null,"abstract":"<p><p>Follicular lymphoma (FL), the second most common subtype of non-Hodgkin lymphoma, relies on interactions with immune elements in the tumor microenvironment, including T-follicular helper cells and follicular dendritic cells, for its survival and progression. Despite its initial responsiveness to chemoimmunotherapy, FL is generally considered incurable. Strategies to improve immune-mediated control of FL could significantly benefit this population, particularly as it includes many elderly and comorbid patients. Immune cell engagers, especially bispecific antibodies (BsAbs), are crucial in targeting FL by bridging tumor and effector cells, thereby triggering T-cell activation and cytotoxic killing. CD3 × CD20 BsAbs have shown the most promise in clinical development for B-NHL patients, with structural variations affecting their target affinity and potency. This review summarizes the current clinical trials of BsAbs for relapsed/refractory FL, highlighting the approval of some agents, their role in first-line treatment or combination therapies, their toxicity profiles, and the future of this therapeutic approach compared to other immune cell therapies.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2412869"},"PeriodicalIF":6.5,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11468044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478269","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":"Benzodiazepines compromise the outcome of cancer immunotherapy.","authors":"Léa Montégut, Lisa Derosa, Meriem Messaoudene, Hui Chen, Flavia Lambertucci, Bertrand Routy, Laurence Zitvogel, Isabelle Martins, Guido Kroemer","doi":"10.1080/2162402X.2024.2413719","DOIUrl":"https://doi.org/10.1080/2162402X.2024.2413719","url":null,"abstract":"<p><p>Acyl CoA binding protein (ACBP, which is encoded by <i>diazepam binding inhibitor</i>, <i>DBI</i>) acts on the gamma-amino butyric acid (GABA) receptor type A via a specific binding site that is shared by diazepam and other benzodiazepines. Both ACBP/DBI and benzodiazepines act as positive allosteric modulators, hence increasing GABA effects on this receptor. Recently, we found that ACBP/DBI acts as an endogenous immunosuppressor, meaning that its antibody-mediated neutralization has immunostimulatory effects and enhances the efficacy of immunotherapy and chemoimmunotherapy in mouse models. Driven by these considerations, we investigated whether diazepam administration in mice would reverse the beneficial effects of ACBP/DBI neutralization on cancer chemoimmunotherapy. Indeed, diazepam abolished the therapeutic of anti-ACBP/DBI antibodies, supporting the idea that diazepam exerts immunosuppressive properties. Of note, treatment with benzodiazepines was associated with poor clinical responses to chemoimmunotherapy in patients with non-small cell lung cancer (NSCLC) as compared to individuals not receiving any psychotropic drugs. Medication with other psychotropic drugs than benzodiazepines did not compromise the outcome of chemoimmunotherapy, indicating that this immunosuppressive effect was benzodiazepine specific. We conclude that benzodiazepines may confer systemic immunosuppression. This hypothesis requires further epidemiological and clinical confirmation.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2413719"},"PeriodicalIF":6.5,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394376","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":"Acyl CoA binding protein (ACBP): an autophagy checkpoint that can be targeted for improving cancer immunosurveillance.","authors":"Léa Montégut, Isabelle Martins, Guido Kroemer","doi":"10.1080/2162402X.2024.2413200","DOIUrl":"10.1080/2162402X.2024.2413200","url":null,"abstract":"<p><p>Acyl CoA binding protein (ACBP) encoded by <i>DBI</i> is a tissue hormone that limits autophagy in multiple cell types, hence acting as an extracellular autophagy checkpoint. We recently reported in <i>Molecular Cancer</i> that monoclonal antibodies neutralizing ACBP improve immunosurveillance of breast and lung carcinomas. Moreover, ACBP neutralization improves the outcome of neoadjuvant chemoimmunotherapy with PD-1 blockade in preclinical models.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2413200"},"PeriodicalIF":6.5,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394375","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}