Cancer immunology research最新文献_第6页

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

Inflammation mediated by gut microbiome alterations promotes lung cancer development and an immunosuppressed tumor microenvironment 肠道微生物组改变介导的炎症促进了肺癌的发展和免疫抑制的肿瘤微环境

IF 10.1 1区医学

Cancer immunology research Pub Date : 2024-09-13 DOI: 10.1158/2326-6066.cir-24-0469

Zahraa Rahal, Yuejiang Liu, Fuduan Peng, Sujuan Yang, Mohamed A. Jamal, Manvi Sharma, Hannah Moreno, Ashish V. Damania, Matthew C. Wong, Mathew C. Ross, Ansam Sinjab, Tieling Zhou, Minyue Chen, Inti Tarifa Reischle, Jiping Feng, Chidera Chukwuocha, Elizabeth Tang, Camille Abaya, Jamie K. Lim, Cheuk Hong Leung, Heather Y. Lin, Nathaniel Deboever, Jack J. Lee, Boris Sepesi, Don L. Gibbons, Jennifer A. Wargo, Junya Fujimoto, Linghua Wang, Joseph F. Petrosino, Nadim J. Ajami, Robert R. Jenq, Seyed Javad Moghaddam, Tina Cascone, Kristi Hoffman, Humam Kadara

{"title":"Inflammation mediated by gut microbiome alterations promotes lung cancer development and an immunosuppressed tumor microenvironment","authors":"Zahraa Rahal, Yuejiang Liu, Fuduan Peng, Sujuan Yang, Mohamed A. Jamal, Manvi Sharma, Hannah Moreno, Ashish V. Damania, Matthew C. Wong, Mathew C. Ross, Ansam Sinjab, Tieling Zhou, Minyue Chen, Inti Tarifa Reischle, Jiping Feng, Chidera Chukwuocha, Elizabeth Tang, Camille Abaya, Jamie K. Lim, Cheuk Hong Leung, Heather Y. Lin, Nathaniel Deboever, Jack J. Lee, Boris Sepesi, Don L. Gibbons, Jennifer A. Wargo, Junya Fujimoto, Linghua Wang, Joseph F. Petrosino, Nadim J. Ajami, Robert R. Jenq, Seyed Javad Moghaddam, Tina Cascone, Kristi Hoffman, Humam Kadara","doi":"10.1158/2326-6066.cir-24-0469","DOIUrl":"https://doi.org/10.1158/2326-6066.cir-24-0469","url":null,"abstract":"Accumulating evidence indicates that the gut microbiome influences cancer progression and therapy. We recently showed that progressive changes in gut microbial diversity and composition are closely associated with tobacco-associated lung adenocarcinoma (LUAD) in a human-relevant mouse model. Furthermore, we demonstrated that the loss of the antimicrobial protein Lcn2 in these mice, exacerbates pro-tumor inflammatory phenotypes while further reducing microbial diversity. Yet, how gut microbiome alterations impinge on LUAD development remains poorly understood. Here, we investigated the role of gut microbiome changes in LUAD development using fecal microbiota transfer and delineated a pathway by which gut microbiome alterations incurred by loss of Lcn2 fostered the proliferation of pro-inflammatory bacteria of the genus Alistipes, triggering gut inflammation. This inflammation propagated systemically, exerting immunosuppression within the tumor microenvironment, augmenting tumor growth through an IL-6-dependent mechanism and dampening response to immunotherapy. Corroborating our preclinical findings, we found that patients with LUAD with a higher relative abundance of Alistipes species in the gut showed diminished response to neoadjuvant immunotherapy. These insights reveal the role of microbiome-induced inflammation in LUAD and present new potential targets for interception and therapy.","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":"72 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256753","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

PTPRZ1-targeting RNA CAR T cells exert antigen-specific and bystander antitumor activity in glioblastoma PTPRZ1 靶向 RNA CAR T 细胞在胶质母细胞瘤中发挥抗原特异性和旁观者抗肿瘤活性

IF 10.1 1区医学

Cancer immunology research Pub Date : 2024-09-13 DOI: 10.1158/2326-6066.cir-23-1094

Darel Martínez Bedoya, Eliana Marinari, Suzel Davanture, Luis Castillo Cantero, Sarah Erraiss, Millicent Dockerill, Sofia Barluenga, Nicolas Winssinger, Karl Schaller, Philippe Bijlenga, Shahan Momjian, Christel Voize, Stéphanie R. Tissot, Lana E. Kandalaft, Philippe Hammel, Pierre Cosson, Paul R. Walker, Valérie Dutoit, Denis Migliorini

{"title":"PTPRZ1-targeting RNA CAR T cells exert antigen-specific and bystander antitumor activity in glioblastoma","authors":"Darel Martínez Bedoya, Eliana Marinari, Suzel Davanture, Luis Castillo Cantero, Sarah Erraiss, Millicent Dockerill, Sofia Barluenga, Nicolas Winssinger, Karl Schaller, Philippe Bijlenga, Shahan Momjian, Christel Voize, Stéphanie R. Tissot, Lana E. Kandalaft, Philippe Hammel, Pierre Cosson, Paul R. Walker, Valérie Dutoit, Denis Migliorini","doi":"10.1158/2326-6066.cir-23-1094","DOIUrl":"https://doi.org/10.1158/2326-6066.cir-23-1094","url":null,"abstract":"The great success of chimeric antigen receptor (CAR) T-cell therapy in the treatment of patients with B-cell malignancies has prompted its translation to solid tumors. In the case of glioblastoma (GBM), clinical trials have shown modest efficacy, but efforts to develop more effective anti-GBM CAR T cells are ongoing. In this study, we selected PTPRZ1 as a target for GBM treatment. We isolated six anti-human PTPRZ1 scFv from a human phage display library and produced 2nd generation CAR T cells in an RNA format. Patient-derived GBM PTPRZ1-knock-in cell lines were used to select the CAR construct that showed high cytotoxicity while consistently displaying high CAR expression (471_28z). CAR T cells incorporating 471_28z were able to release IFN-γ, IL-2, TNF-α, Granzyme B, IL-17A, IL-6, and soluble FasL, and displayed low tonic signaling. Additionally, they maintained an effector memory phenotype after in vitro killing. In addition, 471_28z CAR T cells displayed strong bystander killing against PTPRZ1-negative cell lines after pre-activation by PTPRZ1-positive tumor cells but did not kill antigen-negative non-tumor cells. In an orthotopic xenograft tumor model using NSG mice, a single dose of anti-PTPRZ1 CAR T cells significantly delayed tumor growth. Taken together, these results validate PTPRZ1 as a GBM target and prompt the clinical translation of anti-PTPRZ1 CAR T cells.","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":"75 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256703","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

The Dark Knight: Functional Reprogramming of Neutrophils in the Pathogenesis of Colitis-Associated Cancer 黑暗骑士中性粒细胞在结肠炎相关癌症发病机制中的功能重编程

IF 10.1 1区医学

Cancer immunology research Pub Date : 2024-09-13 DOI: 10.1158/2326-6066.cir-23-0642

Sreya Ghosh, Ivan Zanoni

{"title":"The Dark Knight: Functional Reprogramming of Neutrophils in the Pathogenesis of Colitis-Associated Cancer","authors":"Sreya Ghosh, Ivan Zanoni","doi":"10.1158/2326-6066.cir-23-0642","DOIUrl":"https://doi.org/10.1158/2326-6066.cir-23-0642","url":null,"abstract":"Neutrophils are the primary myeloid cells that are recruited to inflamed tissues, and they are key players during colitis, being also present within the tumor microenvironment during the initiation and growth of colon cancer. Neutrophils fundamentally serve to protect the host against microorganism invasion, but during cancer development, they can become protumoral and lead to tumor initiation, growth, and eventually, metastasis—hence, playing a dichotomic role for the host. Protumoral neutrophils in cancer patients can be immunosuppressive and serve as markers for disease progression but their characteristics are not fully defined. In this review, we explore the current knowledge on how neutrophils in the gut fluctuate between an inflammatory or immunosuppressive state and how they contribute to tumor development. We describe neutrophils’ antitumoral and protumoral effects during inflammatory bowel diseases and highlight their capacity to provoke the advent of inflammation-driven colorectal cancer. We present the functional ambivalence of the neutrophil populations within the colon tumor microenvironment, which can be potentially exploited to establish therapies that will prevent, or even reverse, inflammation-dependent colon cancer incidence in high-risk patients.","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":"67 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256748","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

CD91 and its ligand gp96 confer cross-priming capabilities to multiple APCs during immune responses to nascent, emerging tumors 在对新生肿瘤的免疫反应中，CD91 及其配体 gp96 可赋予多个 APC 相互刺激的能力

IF 10.1 1区医学

Cancer immunology research Pub Date : 2024-09-13 DOI: 10.1158/2326-6066.cir-24-0326

Devanshi A. Nayak, Abigail L. Sedlacek, Anthony R. Cillo, Simon C. Watkins, Robert J. Binder

{"title":"CD91 and its ligand gp96 confer cross-priming capabilities to multiple APCs during immune responses to nascent, emerging tumors","authors":"Devanshi A. Nayak, Abigail L. Sedlacek, Anthony R. Cillo, Simon C. Watkins, Robert J. Binder","doi":"10.1158/2326-6066.cir-24-0326","DOIUrl":"https://doi.org/10.1158/2326-6066.cir-24-0326","url":null,"abstract":"During cancer immunosurveillance, dendritic cells (DCs) play a central role in orchestrating T-cell responses against emerging tumors. Capture of miniscule amounts of antigen along with tumor-initiated costimulatory signals can drive maturation of DCs. Expression of CD91 on DCs is essential in cross-priming of T-cell responses in the context of nascent tumors. Multiple DC and macrophage subsets express CD91 and engage tumor-derived gp96 to initiate antitumor immune responses, yet the specific CD91+ antigen-presenting cells (APCs) that are required for T-cell cross-priming during cancer immunosurveillance are unknown. In this study, we determined that CD91 expression on type 1 conventional DCs (cDC1) is necessary for cancer immunosurveillance. Specifically, CD91-expressing cDC1 were found to capture the CD91 ligand gp96 from tumors and, upon migration to the lymph nodes, distribute gp96 among lymph-node resident APCs. However, cDC1 that captured tumor-derived gp96 only provided early tumor control, while sustained and long-term tumor rejection was bestowed to the host by other gp96+ cross-priming DCs. We further found that the CD91-induced transcriptome in APCs promoted cross-priming of T-cell responses while downregulating immune regulatory pathways. Our results show an elaborate and synchronized division of labor of APCs in the successful elimination of cancer cells via CD91. We predict that the specialized functions of APC subsets can be harnessed for immunotherapy of disease.","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":"202 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256704","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