Cancer immunology research最新文献_第4页

Machine Learning-Directed Conversion of Glioblastoma Cells to Dendritic Cell-Like Antigen-Presenting Cells as Cancer Immunotherapy. 机器学习引导胶质母细胞瘤细胞转化为树突状细胞样抗原递呈细胞，作为癌症免疫疗法。

IF 8.1 1区医学

Cancer immunology research Pub Date : 2024-10-01 DOI: 10.1158/2326-6066.CIR-23-0721

Tianyi Liu, Dan Jin, Son B Le, Dongjiang Chen, Mathew Sebastian, Alberto Riva, Ruixuan Liu, David D Tran

{"title":"Machine Learning-Directed Conversion of Glioblastoma Cells to Dendritic Cell-Like Antigen-Presenting Cells as Cancer Immunotherapy.","authors":"Tianyi Liu, Dan Jin, Son B Le, Dongjiang Chen, Mathew Sebastian, Alberto Riva, Ruixuan Liu, David D Tran","doi":"10.1158/2326-6066.CIR-23-0721","DOIUrl":"10.1158/2326-6066.CIR-23-0721","url":null,"abstract":"Immunotherapy has limited efficacy in glioblastoma (GBM) due to the blood-brain barrier and the immunosuppressed or \"cold\" tumor microenvironment (TME) of GBM, which is dominated by immune-inhibitory cells and depleted of CTL and dendritic cells (DC). Here, we report the development and application of a machine learning precision method to identify cell fate determinants (CFD) that specifically reprogram GBM cells into induced antigen-presenting cells with DC-like functions (iDC-APC). In murine GBM models, iDC-APCs acquired DC-like morphology, regulatory gene expression profile, and functions comparable to natural DCs. Among these acquired functions were phagocytosis, direct presentation of endogenous antigens, and cross-presentation of exogenous antigens. The latter endowed the iDC-APCs with the ability to prime naïve CD8+ CTLs, a hallmark DC function critical for antitumor immunity. Intratumor iDC-APCs reduced tumor growth and improved survival only in immunocompetent animals, which coincided with extensive infiltration of CD4+ T cells and activated CD8+ CTLs in the TME. The reactivated TME synergized with an intratumor soluble PD1 decoy immunotherapy and a DC-based GBM vaccine, resulting in robust killing of highly resistant GBM cells by tumor-specific CD8+ CTLs and significantly extended survival. Lastly, we defined a unique CFD combination specifically for the human GBM to iDC-APC conversion of both glioma stem-like cells and non-stem-like cell GBM cells, confirming the clinical utility of a computationally directed, tumor-specific conversion immunotherapy for GBM and potentially other solid tumors.","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"1340-1360"},"PeriodicalIF":8.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

RNA-encoded Interleukin 2 with Extended Bioavailability Amplifies RNA Vaccine-Induced Antitumor T-cell Immunity. 具有扩展生物利用度的 RNA 编码白细胞介素-2 可增强 RNA 疫苗诱导的抗肿瘤 T 细胞免疫力。

IF 8.1 1区医学

Cancer immunology research Pub Date : 2024-10-01 DOI: 10.1158/2326-6066.CIR-23-0701

Daniel Peters, Lena M Kranz, David Eisel, Mustafa Diken, Sebastian Kreiter, Özlem Türeci, Ugur Sahin, Mathias Vormehr

{"title":"RNA-encoded Interleukin 2 with Extended Bioavailability Amplifies RNA Vaccine-Induced Antitumor T-cell Immunity.","authors":"Daniel Peters, Lena M Kranz, David Eisel, Mustafa Diken, Sebastian Kreiter, Özlem Türeci, Ugur Sahin, Mathias Vormehr","doi":"10.1158/2326-6066.CIR-23-0701","DOIUrl":"10.1158/2326-6066.CIR-23-0701","url":null,"abstract":"Interleukin 2 (IL-2) is a crucial cytokine in T-cell immunity, with a promising potential in cancer vaccines. However, therapeutic application of IL-2 is hampered by its short half-life and substantial toxicity. This study reports preclinical characterization of a mouse serum albumin-IL-2 fusion protein (Alb-IL2) encoded on nucleoside-modified RNA that is delivered via a nanoparticle formulation (Alb-IL2 RNA-NP) mediating prolonged cytokine availability. Alb-IL2 RNA-NP was combined with RNA-lipoplex (RNA-LPX) vaccines to evaluate its effect on the expansion of vaccine-induced antigen specific T-cell immunity. In mice dosed with Alb-IL2 RNA-NP, translated protein was shown to be systemically available up to 2 days, with an albumin-dependent preferred presence in the tumor and tumor-draining lymph node. Alb-IL2 RNA-NP administration prolonged serum availability of the cytokine compared with murine recombinant IL-2. In combination with RNA-LPX vaccines, Alb-IL2 RNA-NP administration highly increased the expansion of RNA-LPX vaccine-induced CD8+ T cells in the spleen and blood. The combination enhanced and sustained the fraction of IL-2 receptor (IL-2R) α-positive antigen-specific CD8+ T cells and ameliorated the functional capacity of the CD8+ T-cell population. Alb-IL2 RNA-NP strongly improved the antitumor activity and survival of concomitant RNA-LPX vaccination and PD-L1 blockade in a subcutaneous mouse tumor model. The favorable pharmacokinetic properties of Alb-IL2 RNA-NP render it an attractive modality for rationally designed combination immunotherapy. RNA vaccines that induce tumor-specific T-cell immunity for Alb-IL2 RNA-NP to further amplify are particularly attractive combination partners.","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"1409-1420"},"PeriodicalIF":8.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141417946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting Tumor-Associated Sialic Acids Using Chimeric Switch Receptors Based on Siglec-9 Enhances the Antitumor Efficacy of Engineered T Cells. 利用基于 Siglec-9 的嵌合开关受体靶向肿瘤相关的 Sialic 酸可增强工程 T 细胞的抗肿瘤功效

IF 8.1 1区医学

Cancer immunology research Pub Date : 2024-10-01 DOI: 10.1158/2326-6066.CIR-23-0823

Vasyl Eisenberg, Shiran Hoogi, Erel Katzman, Nimrod Ben Haim, Raphaelle Zur-Toledano, Maria Radman, Yishai Reboh, Oranit Zadok, Iris Kamer, Jair Bar, Irit Sagi, Ayal Hendel, Cyrille J Cohen

{"title":"Targeting Tumor-Associated Sialic Acids Using Chimeric Switch Receptors Based on Siglec-9 Enhances the Antitumor Efficacy of Engineered T Cells.","authors":"Vasyl Eisenberg, Shiran Hoogi, Erel Katzman, Nimrod Ben Haim, Raphaelle Zur-Toledano, Maria Radman, Yishai Reboh, Oranit Zadok, Iris Kamer, Jair Bar, Irit Sagi, Ayal Hendel, Cyrille J Cohen","doi":"10.1158/2326-6066.CIR-23-0823","DOIUrl":"10.1158/2326-6066.CIR-23-0823","url":null,"abstract":"Cancer exploits different mechanisms to escape T-cell immunosurveillance, including overexpression of checkpoint ligands, secretion of immunosuppressive molecules, and aberrant glycosylation. Herein, we report that IFNγ, a potent immunomodulator secreted in the tumor microenvironment, can induce α2,6 hypersialylation in cancer cell lines derived from various histologies. We focused on Siglec-9, a receptor for sialic acid moieties, and demonstrated that the Siglec-9+ T-cell population displayed reduced effector function. We speculated that Siglec-9 in primary human T cells can act as a checkpoint molecule and demonstrated that knocking out Siglec-9 using a clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system enhanced the functionality of primary human T cells. Finally, we aimed to augment cancer-specific T-cell activity by taking advantage of tumor hypersialylation. Thus, we designed several Siglec-9-based chimeric switch receptors (CSR), which included an intracellular moiety derived from costimulatory molecules (CD28/41BB) and different hinge regions. In an antigen-specific context, T cells transduced with Siglec-9 CSRs demonstrated increased cytokine secretions and upregulation of activation markers. Moreover, T cells equipped with specific Siglec-9 CSRs mediated robust antitumor activity in a xenograft model of human tumors. Overall, this work sheds light on tumor evasion mechanisms mediated by sialylated residues and exemplifies an approach to improve engineered T cell-based cancer treatment. See related Spotlight by Abken, p. 1310.","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"1380-1391"},"PeriodicalIF":8.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transforming the Dark into Light: A Siglec-9 Switch. 化暗为明：Siglec-9 开关。

IF 8.1 1区医学

Cancer immunology research Pub Date : 2024-10-01 DOI: 10.1158/2326-6066.CIR-24-0429

Hinrich Abken

引用次数: 0

A Sampling of Highlights from the Literature. 文献精华选集》。

IF 8.1 1区医学

Cancer immunology research Pub Date : 2024-10-01 DOI: 10.1158/2326-6066.CIR-12-10-WWR

引用次数: 0

The E3 Ubiquitin Ligase FBXO38 Maintains the Antitumor Function of Natural Killer Cells by Sustaining IL15R Signaling. E3泛素连接酶FBXO38通过维持IL-15R信号维持自然杀伤细胞的抗肿瘤功能。

IF 8.1 1区医学

Cancer immunology research Pub Date : 2024-10-01 DOI: 10.1158/2326-6066.CIR-23-1061

Yongjing Shi, Xiaodong Zheng, Hui Peng, Chenqi Xu, Rui Sun, Zhigang Tian, Haoyu Sun, Xianwei Wang

{"title":"The E3 Ubiquitin Ligase FBXO38 Maintains the Antitumor Function of Natural Killer Cells by Sustaining IL15R Signaling.","authors":"Yongjing Shi, Xiaodong Zheng, Hui Peng, Chenqi Xu, Rui Sun, Zhigang Tian, Haoyu Sun, Xianwei Wang","doi":"10.1158/2326-6066.CIR-23-1061","DOIUrl":"10.1158/2326-6066.CIR-23-1061","url":null,"abstract":"Natural killer (NK) cells are the main innate antitumor effector cells but their function is often constrained in the tumor microenvironment. It has been reported that the E3 ligase FBXO38 accelerates PD-1 degradation in tumor-infiltrating T cells to unleash their cytotoxic function. In this study, we found that the transcriptional levels of FBXO38 in intratumoral NK cells of patients with cancer and tumor-bearing mice were significantly lower than in peritumoral NK cells. Conditional knockout of FBXO38 in NK cells accelerated tumor growth and increased tumor metastasis. FBXO38 deficiency resulted in impaired proliferation and survival of tumor-infiltrating NK (TINK) cells. Mechanistically, FBXO38 deficiency enhanced TGF-β signaling, including elevating expression of Smad2 and Smad3, which suppressed expression of the transcription factor Eomes and further reduced expression of surface IL15Rβ and IL15Rγc on NK cells. Consequently, FBXO38 deficiency led to TINK cell hyporesponsiveness to IL15. Consistent with these observations, FBXO38 mRNA expression was positively correlated with the proliferation of TINK cells in multiple human tumors. To study the therapeutic potential of FBXO38, mice bearing human tumors were treated with FBXO38 overexpressed human primary NK cells and showed a significant reduction in tumor size and prolonged survival. In conclusion, our results suggest that FBXO38 sustains NK-cell expansion and survival to promote antitumor immunity and have potential therapeutic implications as they suggest FBXO38 could be harnessed to enhance NK cell-based cancer immunotherapy.","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"1438-1451"},"PeriodicalIF":8.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hypoxia-Induced Long Noncoding RNA HIF1A-AS2 Regulates Stability of MHC Class I Protein in Head and Neck Cancer. 缺氧诱导的长非编码 RNA HIF1A-AS2 调节头颈癌中 MHC I 类蛋白的稳定性

IF 8.1 1区医学

Cancer immunology research Pub Date : 2024-10-01 DOI: 10.1158/2326-6066.CIR-23-0622

Tsai-Tsen Liao, Yu-Hsien Chen, Zih-Yu Li, An-Ching Hsiao, Ya-Li Huang, Ruo-Xin Hao, Shyh-Kuan Tai, Pen-Yuan Chu, Jing-Wen Shih, Hsing-Jien Kung, Muh-Hwa Yang

{"title":"Hypoxia-Induced Long Noncoding RNA HIF1A-AS2 Regulates Stability of MHC Class I Protein in Head and Neck Cancer.","authors":"Tsai-Tsen Liao, Yu-Hsien Chen, Zih-Yu Li, An-Ching Hsiao, Ya-Li Huang, Ruo-Xin Hao, Shyh-Kuan Tai, Pen-Yuan Chu, Jing-Wen Shih, Hsing-Jien Kung, Muh-Hwa Yang","doi":"10.1158/2326-6066.CIR-23-0622","DOIUrl":"10.1158/2326-6066.CIR-23-0622","url":null,"abstract":"Intratumoral hypoxia not only promotes angiogenesis and invasiveness of cancer cells but also creates an immunosuppressive microenvironment that facilitates tumor progression. However, the mechanisms by which hypoxic tumor cells disseminate immunosuppressive signals remain unclear. In this study, we demonstrate that a hypoxia-induced long noncoding RNA HIF1A Antisense RNA 2 (HIF1A-AS2) is upregulated in hypoxic tumor cells and hypoxic tumor-derived exosomes in head and neck squamous cell carcinoma (HNSCC). Hypoxia-inducible factor 1 alpha (HIF1α) was found to directly bind to the regulatory region of HIF1A-AS2 to enhance its expression. HIF1A-AS2 reduced the protein stability of major histocompatibility complex class I (MHC-I) by promoting the interaction between the autophagy cargo receptor neighbor of BRCA1 gene 1 (NBR1) protein and MHC-I, thereby increasing the autophagic degradation of MHC-I. In HNSCC samples, the expression of HIF1A-AS2 was found to correlate with hypoxic signatures and advanced clinical stages. Patients with high HIF1α and low HLA-ABC expression showed reduced infiltration of CD8+ T cells. These findings define a mechanism of hypoxia-mediated immune evasion in HNSCC through downregulation of antigen-presenting machinery via intracellular or externalized hypoxia-induced long noncoding RNA.","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"1468-1484"},"PeriodicalIF":8.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11443317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141449756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Phase 1 Trial of Trebananib, an Angiopoietin 1 and 2 Neutralizing Peptibody, Combined with Pembrolizumab in Patients with Advanced Ovarian and Colorectal Cancer. 血管生成素 1 和 2 中和肽抗体 Trebananib 与 Pembrolizumab 联合治疗晚期卵巢癌和结直肠癌患者的 1 期试验。

IF 8.1 1区医学

Cancer immunology research Pub Date : 2024-09-30 DOI: 10.1158/2326-6066.CIR-23-1027

Brandon M Huffman, Osama E Rahma, Kevin Tyan, Yvonne Y Li, Anita Giobbie-Hurder, Benjamin L Schlechter, Bruno Bockorny, Michael P Manos, Andrew D Cherniack, Joanna Baginska, Adrian Mariño-Enríquez, Katrina Z Kao, Anna K Maloney, Allison Ferro, Sarah Kelland, Kimmie Ng, Harshabad Singh, Emma L Welsh, Kathleen L Pfaff, Marios Giannakis, Scott J Rodig, F Stephen Hodi, James M Cleary

{"title":"A Phase 1 Trial of Trebananib, an Angiopoietin 1 and 2 Neutralizing Peptibody, Combined with Pembrolizumab in Patients with Advanced Ovarian and Colorectal Cancer.","authors":"Brandon M Huffman, Osama E Rahma, Kevin Tyan, Yvonne Y Li, Anita Giobbie-Hurder, Benjamin L Schlechter, Bruno Bockorny, Michael P Manos, Andrew D Cherniack, Joanna Baginska, Adrian Mariño-Enríquez, Katrina Z Kao, Anna K Maloney, Allison Ferro, Sarah Kelland, Kimmie Ng, Harshabad Singh, Emma L Welsh, Kathleen L Pfaff, Marios Giannakis, Scott J Rodig, F Stephen Hodi, James M Cleary","doi":"10.1158/2326-6066.CIR-23-1027","DOIUrl":"https://doi.org/10.1158/2326-6066.CIR-23-1027","url":null,"abstract":"Ovarian cancers and microsatellite stable (MSS) colorectal cancers (CRC) are insensitive to anti-PD1 immunotherapy, and new immunotherapeutic approaches are needed. Preclinical data suggests a relationship between immunotherapy resistance and elevated angiopoietin 2 levels. We performed a phase 1 dose-escalation study of pembrolizumab and the angiopoietin 1/2 inhibitor trebananib (NCT03239145). This multicenter trial enrolled patients with metastatic ovarian cancer or MSS CRC. Trebananib was administered intravenously weekly for 12 weeks with 200 mg intravenous pembrolizumab every 3 weeks. The toxicity profile of this combination was manageable, and the protocol-defined highest dose level (trebananib 30 mg/kg weekly plus pembrolizumab 200 mg every 3 weeks) was declared the maximum tolerated dose. The objective response rate for all patients was 7.3% (90% confidence interval: 2.5-15.9%). Three patients with MSS CRC had durable responses for ≥3 years. One responding patient's CRC harbored a POLE mutation. The other two responding patients had left-sided CRCs with no baseline liver metastases, and genomic analysis revealed that they both had KRAS wild-type, ERBB2 amplified tumors. After development of acquired resistance, biopsy of one patient's KRAS wild-type, ERBB2 amplified tumor showed a substantial decline in tumor-associated T cells and an increase in immunosuppressive intratumoral macrophages. Future studies are needed to carefully assess whether clinicogenomic features, such as lack of liver metastases, ERBB2 amplification, and left-sided tumors, can predict increased sensitivity to PD1 immunotherapy combinations.","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deleting Trim33 in myeloid cells improves the efficiency of radiotherapy through an interferon beta dependent anti-tumor immune response. 通过干扰素 beta 依赖性抗肿瘤免疫反应，删除骨髓细胞中的 Trim33 可提高放疗效率。

IF 8.1 1区医学

Cancer immunology research Pub Date : 2024-09-26 DOI: 10.1158/2326-6066.CIR-24-0026

Anaïs Assouvie, Marine Gerbé De Thoré, Claire Torres, Véronique Ménard, Alexia Alfaro, Eric Deutsch, Michele Mondini, Germain Rousselet

{"title":"Deleting Trim33 in myeloid cells improves the efficiency of radiotherapy through an interferon beta dependent anti-tumor immune response.","authors":"Anaïs Assouvie, Marine Gerbé De Thoré, Claire Torres, Véronique Ménard, Alexia Alfaro, Eric Deutsch, Michele Mondini, Germain Rousselet","doi":"10.1158/2326-6066.CIR-24-0026","DOIUrl":"https://doi.org/10.1158/2326-6066.CIR-24-0026","url":null,"abstract":"Radiotherapy (RT) triggers an immune response that contributes to anti-tumor effects. Induction of interferon beta (IFN-β) is a key event in this immunogenicity of RT. We have previously shown that TRIM33, a chromatin reader, restrains IFN-β expression in Toll-like receptor-activated myeloid cells. Here, we explored whether deleting Trim33 in myeloid cells might improve the radio-induced immune response, and subsequent efficiency of RT. We first established that Trim33-/- bone marrow-derived macrophages showed increased expression of IFN-β in response to direct irradiation, or to treatment with irradiated cancer cells, further supporting our hypothesis. We then tested the efficiency of a single dose RT in three subcutaneous and one orthotopic tumor models. In all situations, myeloid deletion of Trim33 led to a significantly improved response after RT, leading to a complete and durable response in most of the treated mice bearing orthotopic oral tumors. This effect required the IFN-I pathway, and the presence of CD8+ T lymphocytes, but not NK cells. In addition, cured mice were capable of rejecting a secondary tumor challenge, demonstrating an in situ vaccination effect. We conclude that deleting Trim33 in myeloid cells improves RT efficiency, through a mechanism involving the IFN-I pathway and the immune response. Our work suggests that myeloid Trim33 is a host factor affecting the tumor response to RT, thus representing a new potential therapeutic target for modifying RT responses.","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hyper-Interferon Sensitive influenza induces adaptive immune responses and overcomes resistance to anti-PD-1 in murine non-small cell lung cancer. 超干扰素敏感性流感诱导适应性免疫反应，克服小鼠非小细胞肺癌对抗 PD-1 的耐药性。

IF 8.1 1区医学

Cancer immunology research Pub Date : 2024-09-26 DOI: 10.1158/2326-6066.CIR-23-1075

Yushen Du, Ramin Salehi-Rad, Tian-Hao Zhang, William P Crosson, Jensen Abascal, Dongdong Chen, Yuan Shi, Hong Jiang, Yen-Wen Tseng, Xi Ma, Mengying Hong, Sihan Wang, Xijuan Wang, Kejun Tang, Shiyao Hu, Yuting Li, Shaokai Ni, Yiqi Cai, Shahed Tappuni, Yong Shen, Bin Liu, Ren Sun

{"title":"Hyper-Interferon Sensitive influenza induces adaptive immune responses and overcomes resistance to anti-PD-1 in murine non-small cell lung cancer.","authors":"Yushen Du, Ramin Salehi-Rad, Tian-Hao Zhang, William P Crosson, Jensen Abascal, Dongdong Chen, Yuan Shi, Hong Jiang, Yen-Wen Tseng, Xi Ma, Mengying Hong, Sihan Wang, Xijuan Wang, Kejun Tang, Shiyao Hu, Yuting Li, Shaokai Ni, Yiqi Cai, Shahed Tappuni, Yong Shen, Bin Liu, Ren Sun","doi":"10.1158/2326-6066.CIR-23-1075","DOIUrl":"10.1158/2326-6066.CIR-23-1075","url":null,"abstract":"Despite recent advances in immunotherapy with immune checkpoint inhibitors (ICI), many patients with non-small cell lung cancer (NSCLC) fail to respond or develop resistance after an initial response. In situ vaccination (ISV) with engineered viruses has emerged as a promising antigen-agnostic strategy that can both condition the tumor microenvironment (TME) and augment anti-tumor T cell responses to overcome immune resistance. We engineered a live attenuated viral vaccine, Hyper-Interferon Sensitive virus (HIS), by conducting a genome-wide functional screening and introducing eight interferon (IFN)-sensitive mutations in the influenza genome. Compared to wild-type (WT) influenza, HIS replication was attenuated in immunocompetent hosts, enhancing its potential as a safe option for cancer therapy. HIS ISV elicited robust yet transient type I IFN responses in murine NSCLCs, leading to an enrichment of polyfunctional effector Th1 CD4 and cytotoxic CD8 T cells into the tumor. HIS ISV demonstrated enhanced anti-tumor efficacy compared to WT in multiple syngeneic murine models of NSCLC with distinct driver mutations and varying mutational burden. This efficacy was dependent on host type 1 IFN responses and T lymphocytes. HIS ISV overcame resistance to anti-PD-1 in LKB-1 deficient murine NSCLC, resulting in improved overall survival and enduring systemic tumor-specific immunity. These studies provide compelling evidence to support further clinical evaluation of HIS as a novel 'off-the-shelf' ISV strategy for patients with NSCLC refractory to ICI.","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0