Oncoimmunology最新文献

{"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":"Pre-radiation Nivolumab plus ipilimumab in patients with newly diagnosed high-grade gliomas.","authors":"Santosh Kesari, Alexandre Wojcinski, Sarabjot Pabla, R J Seager, Jaya M Gill, Jose A Carrillo, Naveed Wagle, David J Park, Minhdan Nguyen, Judy Truong, Yuki Takasumi, Lisa Chaiken, Shu-Ching Chang, Garni Barkhoudarian, Daniel F Kelly, Tiffany M Juarez","doi":"10.1080/2162402X.2024.2432728","DOIUrl":"10.1080/2162402X.2024.2432728","url":null,"abstract":"<p><p>The limited success of immune checkpoint inhibitors (ICIs) in the adjuvant setting for glioblastoma highlights the need to explore administering ICIs prior to immunosuppressive radiation. To address the feasibility and safety of this approach, we conducted a phase I study in patients with newly diagnosed Grade 3 and Grade 4 gliomas. Patients received nivolumab 300 mg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks until disease progression or unacceptable toxicity. Fifteen patients were treated, with four patients on dexamethasone at treatment initiation and five tumors having <i>MGMT</i> promoter methylated. Treatment began a median of 38 days post-surgery. The most common treatment-related adverse events (AEs) were rash, pruritus, fatigue, nausea, and anorexia. Grade 3 AEs were lipase increased (<i>n</i> = 2), anorexia (<i>n</i> = 1), pruritus (<i>n</i> = 1), and rash (<i>n</i> = 3), and one Grade 4 cerebral edema occurred. Median progression-free survival (mPFS) was 1.3 months and median overall survival (mOS) was 19.3 months (95% CI, 12.9-NA). Three patients deferred conventional radiochemotherapy for over seven months while ten eventually received it. Progressing tumors tended to exhibit higher LAG-3 levels at baseline compared to shrinking tumors. Analysis of paired pre-treatment and post-progression tissue (<i>n</i> = 5) showed trends of up-regulated TGF-β, ERBB2, ERBB3, and ERBB4 signaling pathways, downregulated PPAR signaling, decreased B cell proportions, and increased monocytes proportions in tumors post-treatment. We show nivolumab plus ipilimumab can be safely administered prior to standard radiotherapy for newly diagnosed gliomas and is operationally feasible. Clinicaltrials.gov NCT03425292 registered February 7, 2018.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2432728"},"PeriodicalIF":6.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of B7-H3 expression on metastasis, immune exhaustion and JAK/STAT and PI3K/AKT pathways in clear cell renal cell carcinoma.","authors":"Maite Emaldi, Esther Rey-Iborra, Ángela Marín, Lorena Mosteiro, David Lecumberri, Tove Øyjord, Noémie Roncier, Gunhild M Mælandsmo, Javier C Angulo, Peio Errarte, Gorka Larrinaga, Rafael Pulido, José I López, Caroline E Nunes-Xavier","doi":"10.1080/2162402X.2024.2419686","DOIUrl":"https://doi.org/10.1080/2162402X.2024.2419686","url":null,"abstract":"<p><p>Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors (TKIs) are improving the response rates of advanced renal cancer patients. However, many treated patients do not respond, making novel immune checkpoint-based immunotherapies potentially clinically beneficial only for specific groups of patients. We detected high expression of the immune checkpoint protein B7-H3 in clear cell renal cell carcinomas (ccRCCs) and evaluated B7-H3 immunohistochemistry staining in tissue microarray samples from two distinct renal cancer cohorts. B7-H3 was highly expressed in approximately 50% of primary tumors and in 30% of metastatic lesions. B7-H3 expression in primary tumors correlated with tumor necrosis, sarcomatoid transformation, disease-free survival, and synchronous metastasis, while B7-H3 expression in metastasis correlated with metastases to the lymph nodes. Gene expression analysis revealed the association of B7-H3 expression with gene expression scores involved in T cell exhaustion and myeloid immune evasion, as well as with PI3K/AKT and JAK/STAT pathways. Furthermore, knocking down B7-H3 expression in renal cancer cells by siRNA and CRISPR/Cas resulted in lower 2D and 3D cell proliferation and viability as well as increased sensitivity to TKI axitinib. Together, our findings suggest a pro-oncogenic and immune evasive role for B7-H3 in ccRCC and highlight B7-H3 as an actionable novel immune checkpoint protein in combination with TKI in advanced renal cancer.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2419686"},"PeriodicalIF":6.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142773963","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":"High circulating HMGB1 indicates good prognosis in patients with advanced leiomyosarcoma under chemoimmunotherapy.","authors":"Lucillia Bezu, Guido Kroemer","doi":"10.1080/2162402X.2024.2432059","DOIUrl":"10.1080/2162402X.2024.2432059","url":null,"abstract":"<p><p>Few clinical studies investigated the putative link between the activation of immunogenic cell death (ICD) and the oncological outcome. Recent data, published in a Phase 1b trial, demonstrated that an ICD-associated surge in the plasma concentration of high-mobility group box 1 (HMGB1) indicates favorable prognosis in patients with advanced leiomyosarcomas treated with the combination of doxorubicin, dacarbazine and nivolumab.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2432059"},"PeriodicalIF":6.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689286","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":"RIPK1 inhibition in malignant cells potentiates immunotherapy and radiotherapy outcome.","authors":"Jonathan G Pol, Andrea Checcoli, Manuela Lizarralde-Guerrero, Guido Kroemer","doi":"10.1080/2162402X.2024.2425465","DOIUrl":"10.1080/2162402X.2024.2425465","url":null,"abstract":"<p><p>Apoptosis, necroptosis and pro-inflammatory NF-κB-dependent signaling are repressed by receptor-interacting serine/threonine-protein kinase 1 (RIPK1). A recent paper in <i>Immunity</i> describes a small molecule inducing the proteolytic degradation of RIPK1. In preclinical experiments, this RIPK1 inhibitor improved the anticancer efficacy of radiotherapy, immunotherapy (with PD-1 blockade) and radioimmunotherapy (with CTLA-4 blockade).</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2425465"},"PeriodicalIF":6.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711679","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":"Regional immune mechanisms enhance efficacy of an autologous cellular cancer vaccine with intraperitoneal administration.","authors":"Ben Marwedel, Lorél Y Medina, Henning De May, Joshua E Adogla, Ellie Kennedy, Erica Flores, Eunju Lim, Sarah Adams, Eric Bartee, Rita E Serda","doi":"10.1080/2162402X.2024.2421029","DOIUrl":"10.1080/2162402X.2024.2421029","url":null,"abstract":"<p><p>Widespread peritoneal dissemination is common in patients with gynecologic or gastrointestinal cancers. Accumulating evidence of a central role for regional immunity in cancer control indicates that intraperitoneal immunotherapy may have treatment advantages. This study delineates immune mechanisms engaged by intraperitoneal delivery of a cell-based vaccine comprised of silicified ovarian cancer cells associated with enhanced survival. Vaccine trafficking from the site of injection to milky spots and other fat-associated lymphoid clusters was studied in syngeneic cancer models using bioluminescent and fluorescent imaging, microscopy, and flow cytometry. Spectral flow cytometry was used to phenotype peritoneal immune cell populations, while bioluminescent imaging of cancer was used to study myeloid and T cell dependency, systemic immunity, and vaccine efficacy in models of disseminated high-grade serous ovarian and DNA mismatch-repair proficient microsatellite-stable colorectal cancer. Following intraperitoneal vaccination of mice with ovarian cancer, vaccine cells were rapidly internalized by myeloid cells, with subsequent trafficking to fat-associated lymphoid clusters. Tumor clearance was confirmed to be T cell-mediated, leading to the establishment of local and systemic immunity. Combination immune checkpoint inhibitor and vaccine therapy in mice with advanced disease, characterized by an established suppressive tumor microenvironment, increased the number of mice with non-detectable tumors, however, change in tumor burden compared to vaccine monotherapy was not significant. Vaccination also resulted in tumor clearance in mouse models of metastatic colorectal cancer. This study demonstrates that intraperitoneal vaccine delivery has the potential to enhance vaccine efficacy by activating resident immune cells with the subsequent establishment of protective systemic anti-tumor immunity.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2421029"},"PeriodicalIF":6.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142773966","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":"Cell therapy for a rare disease- hairy cell leukemia variant.","authors":"Claire Fritz, Derek P Wong, Philip Rock, Richard Burack, Akshaya Radhakrishnan, Reshmi Parameswaran","doi":"10.1080/2162402X.2024.2432062","DOIUrl":"10.1080/2162402X.2024.2432062","url":null,"abstract":"<p><p>Hairy cell leukemia variant (HCL-v) is a rare malignancy of clonal mature B-cells that follows a chronic disease course. HCL-v patients are often resistant to purine nucleoside analogs, which are the first-line therapy. To address the shortcomings of current therapy for HCL-v, we investigated the activity of a BAFF ligand-based CAR-T cell which binds to all three BAFF receptors, BAFF-receptor, TACI, and BCMA. Here, we demonstrate that HCLv patient-derived cells highly express all three BAFF receptors and that BAFF CAR-T cells induce significant cytotoxicity in vitro against both cell lines and HCL-v patient cells. This cytotoxicity corresponds with significant CAR-T cell activation, degranulation, and release of pro-inflammatory cytokines after co-incubation with HCLv cells. Furthermore, we successfully generated BAFF CAR-T cells directly from an HCLv patient and observed direct autologous killing against patient tumor cells in vitro. These HCLv patient-derived CAR-T cells were also effective in killing the Hair-M cell line and tumor cells derived from a different HCLv patient. Lastly, we also developed two mouse xenograft models for HCL, a subcutaneous Bonna-12 model and intravenous Hair-M xenograft model. We observed decreases in tumor burden and prolonged overall survival without significant toxicity. In conclusion, here we show that BAFF CAR-T cells exert anti-tumor effects in vitro and in vivo against multiple cell lines and patient-derived HCL-v samples and may be a successful therapeutic strategy for HCLv patients.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2432062"},"PeriodicalIF":6.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11610546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741039","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":"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}