Juheon Lee, Jinhoo Song, Wonbeak Yoo, Hyunji Choi, Dana Jung, Eunjeong Choi, Seo-Gyeong Jo, Eun-Yeung Gong, Young-Hee Jeoung, You-Soo Park, Woo-Chang Son, Hosuk Lee, Hayoung Lee, Jeom Ji Kim, TaeEun Kim, Sooyun Lee, Jang-June Park, Tae-Don Kim, Seok-Ho Kim
{"title":"Therapeutic potential of anti-ErbB3 chimeric antigen receptor natural killer cells against breast cancer.","authors":"Juheon Lee, Jinhoo Song, Wonbeak Yoo, Hyunji Choi, Dana Jung, Eunjeong Choi, Seo-Gyeong Jo, Eun-Yeung Gong, Young-Hee Jeoung, You-Soo Park, Woo-Chang Son, Hosuk Lee, Hayoung Lee, Jeom Ji Kim, TaeEun Kim, Sooyun Lee, Jang-June Park, Tae-Don Kim, Seok-Ho Kim","doi":"10.1007/s00262-024-03923-y","DOIUrl":"10.1007/s00262-024-03923-y","url":null,"abstract":"<p><p>ErbB3 is markedly overexpressed in breast cancer cells and is associated with resistance and metastasis. Additionally, ErbB3 expression levels are positively correlated with low densities of tumor-infiltrating lymphocytes, a marker of poor prognosis. Consequently, ErbB3 is a promising therapeutic target for cancer immunotherapy. Here, we report the generation of ErbB3-targeted chimeric antigen receptor (CAR)-modified natural killer (NK) cells by transducing cord blood-derived primary NK cells using vsv-g envelope-pseudotyped lentiviral vectors. Transduced cells displayed stable CAR-expressing activity and increased cytotoxicity against ErbB3-positive breast cancer cell lines. Furthermore, anti-ErbB3 (aErbB3) CAR-NK cells strongly reduced the tumor burden in the SK-BR-3 xenograft mouse model without observable side effects. These findings underscore the potential of aErbB3 CAR-NK cells as targeted immunotherapy for ErbB3-positive breast cancer, suggesting a promising alternative to conventional treatments.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 2","pages":"73"},"PeriodicalIF":4.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11698710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920733","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":"Efficacy and safety of PD-1 blockade-activated neoantigen specific cellular therapy for advanced relapsed non-small cell lung cancer.","authors":"Yun Qiao, Kaiyuan Hui, Chenxi Hu, Mei Wang, Wen Sun, Liang Liu, Changhong Dong, Xiaodong Jiang","doi":"10.1007/s00262-024-03906-z","DOIUrl":"10.1007/s00262-024-03906-z","url":null,"abstract":"<p><strong>Background: </strong>Due to its strong immunogenicity and tumor specificity, neoplastic antigen has emerged as an immunotherapy target with wide therapeutic prospect and clinical application value. Anti-programmed death-1 (PD-1) antibodies reinvigorate T cell-mediated antitumor immunity. So, we conducted single-arm trial to assess the safety and efficacy of PD-1 blockade(Camrelizumab)-activated neoantigen specific cellular therapy (aNASCT) on advanced relapsed non-small lung cancer(NSCLC)(ClinicalTrials.gov NCT03205930).</p><p><strong>Methods: </strong>Neoantigenic peptides were designed and manufactured according to the whole exome sequencing and RNA sequencing of fresh biopsy tissues and peripheral blood as well as bioinformatics analysis. All participants received subcutaneous injection of mature dendritic cells(mDCs) loaded with neoantigens on day 8 and an intravenous infusion of PD-1 blockade-activated autologous cytotoxic T lymphocytes (CTLs) induced by mDCs on day 27 for a period defined as 28 days (4 weeks). Enrolled patients received at least three cycles of therapy. The safety and efficacy of the treatment were evaluated by evaluating adverse reactions, progression-free survival (PFS), overall survival (OS).</p><p><strong>Results: </strong>A total of 13 patients with advanced relapsed NSCLC were enrolled in this study. All 13 patients received at least three cycles of aNASCT treatment, of which two patients received at most 12 cycles of treatment. Treatment-related adverse events (AEs) occurred in 4/13 (30.8%)patients with transient fever below 38℃.The objective response rate (ORR) across the 13 enrolled patients was 7 of 13 (53.85%,95% CI 0.29-0.77).The disease control rate (DCR) was 8 of 13 (61.54%,95% CI 0.36-0.82). The median PFS was 11 months (95% CI 6.1-15.9), and the median OS was 15 months(95% CI 11.5-18.5).</p><p><strong>Conclusions: </strong>Our findings indicate that aMASCT therapy was safety and immunogenicity of patients with advanced relapsed NSCLC, suggesting its promising potential in cancer immunotherapy.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 2","pages":"60"},"PeriodicalIF":4.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920475","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":"Sex differences in immunotherapy outcomes and tumor-infiltrating immune cell profiles in patients with advanced renal cell carcinoma.","authors":"Hiroki Ishihara, Hironori Fukuda, Yukihiro Mizoguchi, Makiko Yamashita, Kazunori Aoki, Ryo Ishiyama, Takashi Ikeda, Yuki Nemoto, Hiroaki Shimmura, Yasunobu Hashimoto, Kazuhiko Yoshida, Toshihito Hirai, Junpei Iizuka, Daisuke Tokita, Tsunenori Kondo, Yoji Nagashima, Toshio Takagi","doi":"10.1007/s00262-024-03876-2","DOIUrl":"10.1007/s00262-024-03876-2","url":null,"abstract":"<p><p>Sex differences in the outcomes of advanced renal cell carcinoma (RCC) treated with immune checkpoint inhibitors (ICIs) and the profiles of tumor-infiltrating immune cells (TIICs) remain unclear. We retrospectively evaluated data from 563 patients with RCC receiving systemic therapy, including first-line dual ICI combinations (i.e., immunotherapy [IO]-IO), combinations of ICIs with tyrosine kinase inhibitors (TKIs) (i.e., IO-TKI), TKI monotherapy, and subsequent nivolumab monotherapy. Survival and tumor response were compared between the sexes in each treatment group, and TIIC profiles were compared using 116 RCC tumor samples analyzed by flow cytometry. Progression-free survival (PFS) was shorter in female than in male patients in the IO-IO (p = 0.0227) and nivolumab monotherapy (p = 0.0478) groups. Furthermore, sex remained an independent factor for shorter PFS after adjusting for covariates in the IO-IO (p = 0.0340) and nivolumab monotherapy (p = 0.0322) groups. In contrast, PFS was not significantly different between sexes in the IO-TKI or TKI monotherapy groups (p > 0.05). Overall survival and objective response rates were not significantly different between the sexes in any of the treatment groups (p > 0.05). Some TIIC populations, including that of CD8 + T cells (p = 0.0096), decreased to a greater extent in female than in male patients in the advanced-stage population. In conclusion, the effectiveness of ICIs on PFS was lower in female patients than in male patients, potentially because of the different profiles of the immune microenvironment, particularly the decreased number of CD8 + T cells in females.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 2","pages":"51"},"PeriodicalIF":4.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920660","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":"Understanding the impact of spatial immunophenotypes on the survival of endometrial cancer patients through the ProMisE classification.","authors":"Satomi Hattori, Nobuhisa Yoshikawa, Wenting Liu, Tetsuya Matsukawa, Mei Kubokawa, Kosuke Yoshida, Masato Yoshihara, Satoshi Tamauchi, Yoshiki Ikeda, Akira Yokoi, Yusuke Shimizu, Kaoru Niimi, Hiroaki Kajiyama","doi":"10.1007/s00262-024-03919-8","DOIUrl":"10.1007/s00262-024-03919-8","url":null,"abstract":"<p><strong>Objectives: </strong>We focused on how the immunophenotypes based on the distribution of CD8-positive tumor-infiltrating lymphocytes (TILs) relate to the endometrial cancer (EC) molecular subtypes and patients' prognosis.</p><p><strong>Patients and methods: </strong>Two cohorts of EC patients (total n = 145) were analyzed and categorized using the Molecular Risk Classifier for Endometrial cancer (ProMisE): POLEmut (POLE mutation), MMRd (mismatch repair deficiency), NSMP (no specific molecular profile), and p53abn (p53 abnormality). CD8-positive TILs, within the central tumor and the invasive margin, were examined by using immunohistochemical staining and advanced image-analysis software. It was investigated whether these immunophenotypes correlate with the molecular subtypes and patients' survival. RNA-sequencing (RNA-seq) was used to explore tumor-derived factors influencing these immunophenotypes.</p><p><strong>Results: </strong>Three distinct immunophenotypes (inflamed, excluded, and desert) based on the CD8-positive TIL patterns were identified in EC patients. Notably, the inflamed phenotype was most frequently observed in the POLEmut and MMRd subtypes, while the desert phenotype was predominant in the NSMP subtype; however, other immunophenotypes were also observed. All p53abn subtype showed the non-inflamed (excluded or desert) phenotype. The prognosis was markedly poorer in the patients with the non-inflamed phenotype than in those with the inflamed phenotype. The RNA-seq analysis showed that the expression of MYC target genes and type-1 interferon response genes was enriched in the non-inflamed phenotype in MMRd and NSMP subtypes, respectively.</p><p><strong>Conclusion: </strong>Evaluating not only the molecular classification but also the immunophenotype may lead to more personalized immunotherapy in EC and elucidating the mechanisms that underlie the formation of the three immunophenotypes could lead to the discovery of new immunotherapy targets.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 2","pages":"70"},"PeriodicalIF":4.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920767","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}
Lv Guangzhao, Wang Xin, Wu Miaoqing, Ma Wenjuan, Liu Ranyi, Pan Zhizhong, Zhang Rongxin, Chen Gong
{"title":"IDO1 inhibitor enhances the effectiveness of PD-1 blockade in microsatellite stable colorectal cancer by promoting macrophage pro-inflammatory phenotype polarization.","authors":"Lv Guangzhao, Wang Xin, Wu Miaoqing, Ma Wenjuan, Liu Ranyi, Pan Zhizhong, Zhang Rongxin, Chen Gong","doi":"10.1007/s00262-024-03925-w","DOIUrl":"10.1007/s00262-024-03925-w","url":null,"abstract":"<p><p>Microsatellite stable (MSS) colorectal cancer (CRC) is a subtype of CRC that generally exhibits resistance to immunotherapy, particularly immune checkpoint inhibitors such as PD-1 blockade. This study investigates the effects and underlying mechanisms of combining PD-1 blockade with IDO1 inhibition in MSS CRC. Bioinformatics analyses of TCGA-COAD and TCGA-READ cohorts revealed significantly elevated IDO1 expression in CRC tumors, correlating with tumor mutation burden across TCGA datasets. In vivo experiments demonstrated that the combination of IDO1 inhibition and PD-1 blockade significantly reduced tumor growth and increased immune cell infiltration, particularly pro-inflammatory macrophages and CD8+ T cells. IDO1 knockdown in CRC cell lines impaired tolerance to interferon-γ and increased apoptosis in vitro, which were rescued by the application of kynurenine, the end product of IDO1. IDO1 knockdown in MSS CRC enhanced the effectiveness of PD-1 blockade therapy in vivo. IDO1 knockdown cancer cells promoted pro-inflammatory macrophage polarization and enhanced phagocytic activity in vitro, associated with the upregulation of JAK2-STAT3-IL6 signaling pathway. These findings highlight the role of IDO1 in modulating the tumor immune microenvironment in MSS CRC and suggest that combining PD-1 blockade with IDO1 inhibition could enhance therapeutic efficacy by promoting macrophage pro-inflammatory polarization and infiltration through the JAK2-STAT3-IL6 pathway.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 2","pages":"71"},"PeriodicalIF":4.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920617","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}
Mark K Farrugia, Elizabeth A Repasky, Minhui Chen, Kristopher Attwood, Kayla Catalfamo, Hanna Rosenheck, Song Yao, David M Mattson, Sarbajit Mukherjee, Moshim Kukar, Agnieszka K Witkiewicz, Anurag K Singh
{"title":"Prognostic immune markers in esophageal cancer patients managed with trimodal therapy.","authors":"Mark K Farrugia, Elizabeth A Repasky, Minhui Chen, Kristopher Attwood, Kayla Catalfamo, Hanna Rosenheck, Song Yao, David M Mattson, Sarbajit Mukherjee, Moshim Kukar, Agnieszka K Witkiewicz, Anurag K Singh","doi":"10.1007/s00262-024-03891-3","DOIUrl":"10.1007/s00262-024-03891-3","url":null,"abstract":"<p><strong>Background: </strong>Esophageal cancer (ESC) is an aggressive disease which often presents at an advanced stage. Despite trimodal therapy, 40-50% patients can develop metastatic disease by 18 months. Identification of patients at risk for metastatic spread is challenging with need for improved prognostication. We investigated whether the immune landscape of pretreatment tissue was associated with relapse in ESC patients.</p><p><strong>Methods: </strong>Between April 2010 and October 2018, we identified 25 patients who had undergone trimodal therapy for ESC and had pretreatment biopsies suitable for analyses. We performed high-throughput multispectral immunofluorescence (mIF) analysis on formalin-fixed paraffin embedded biopsy samples. Analysis of 27 unique populations via immune and exhaustion mIF panels was performed and expression was normalized to total cell counts.</p><p><strong>Results: </strong>Of the 25 patients analyzed, the median follow-up time was 23.9 months, during which 12 (48%) patients suffered a relapse with a median time to progression of 13.1 months. mIF revealed higher expression of HLA-DR (p = 0.019), CD8/LAG3 (p = 0.046), and CD8/CTLA4 (p = 0.027) among patients without relapse. Time to progression (TTP) and disease-specific survival (DSS) were stratified by median expression of each significant subpopulation and formally tested by the log-rank test. Higher than median expression of HLA-DR (p = 0.027), CD8/LAG3 (p = 0.039), and CD8/CTLA4 (p = 0.039) were significantly associated with TTP. Similarly, HLA-DR (p = 0.0069) and CD8/CTLA4 (p = 0.036) were significantly associated with improved DSS, whereas no significant observations were found with CD8/LAG3 (p = 0.11) expression. Stromal, but not tumoral expression of CD163 and CD163/PDL1 were significantly associated with improved TTP and DSS.</p><p><strong>Conclusions: </strong>High expression of HLA-DR, CD8/CTLA4, and stromal expression of CD163 and CD163/PDL1 within pretreatment biopsy ESC samples was associated with significantly reduced rates of relapse. Increased presence of these markers suggests that an improved immune landscape is associated with less aggressive disease and may provide an opportunity for risk-based treatment strategies.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 2","pages":"57"},"PeriodicalIF":4.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11698998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920622","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":"TDO2 + cancer-associated fibroblasts mediate cutaneous squamous cell carcinoma immune escape via impeding infiltration of CD8 + T cells.","authors":"Fangqi Lu, Guorong Yan, Zijun Zhao, Zhe Zheng, Yuhao Wu, Long Wen, Yeqaing Liu, Qingyu Zeng, Guolong Zhang","doi":"10.1007/s00262-024-03921-0","DOIUrl":"10.1007/s00262-024-03921-0","url":null,"abstract":"<p><p>Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer, originating from the malignant proliferation of squamous epithelial cells. However, its pathogenesis remains unclear. To further explore the mechanisms underlying cSCC, we analyzed the data from one single-cell RNA sequencing study and discovered a significant upregulation of tryptophan 2,3-dioxygenase (TDO2) in the cancer-associated fibroblasts (CAFs). Nonetheless, the specific expression and potential biological significance of TDO2 in cSCC have not yet been reported. In this study, we confirmed that TDO2 is highly expressed in CAFs of cSCC. Clinical correlation analysis indicated that high TDO2 expression was significantly associated with poor tumor differentiation. Furthermore, increased TDO2 expression in cSCC correlated with reduced CD8 + T cell infiltration, suggesting its role in modulating immune responses. TDO2 inhibitors significantly reduced the size and number of tumors in mice and effectively increased CD8 + T cell infiltration. RNA sequencing analysis revealed that TDO2 inhibitors modulate immune cell activity and downregulate the PI3K-Akt signaling pathway. In summary, our study demonstrates that TDO2 + CAFs induce immune evasion by inhibiting CD8 + T cell infiltration in cSCC. Inhibiting TDO2 could enhance antitumor immune responses, providing a promising strategy to improve treatment outcomes in cSCC.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 2","pages":"67"},"PeriodicalIF":4.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11698999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920728","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":"CircRNA-loaded DC vaccine in combination with low-dose gemcitabine induced potent anti-tumor immunity in pancreatic cancer model.","authors":"Zongyu Cai, Qimuge Wuri, Yang Song, Xueli Qu, Haotong Hu, Simiao Cao, Hui Wu, Jiaxin Wu, Chu Wang, Xianghui Yu, Wei Kong, Haihong Zhang","doi":"10.1007/s00262-024-03924-x","DOIUrl":"10.1007/s00262-024-03924-x","url":null,"abstract":"<p><p>Although promising, dendritic cell (DC) vaccines may not suffice to fully inhibit tumor progression alone, mainly due to the short expression time of the antigen in DC vaccines, immunosuppressive tumor microenvironment, and tumor antigenic modulation. Overcoming the limitations of DC vaccines is expected to further enhance their anti-tumor effects. In this study, we constructed a circRNA-loaded DC vaccine utilizing the inherent stability of circular RNA to enhance the expression level and duration of the antigen within the DC vaccine. Meanwhile we combined it with gemcitabine and validated their therapeutic efficacy in the Panc02 tumor model. We found that the use of DC vaccine alone can reach a tumor inhibition rate of 69%, and the effect was further enhanced when combined with gemcitabine, reaching a tumor inhibition rate of 89%. The combined treatment achieved a synergistic effect, which not only reduced immunosuppressive Tregs but also induced immunogenic cell death, leading to antigen spreading and reducing immune evasion caused by tumor antigenic modulation. As a result, the survival of the mice was significantly prolonged. Our research provides a promising approach for the clinical treatment of pancreatic cancer.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 2","pages":"68"},"PeriodicalIF":4.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920908","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}
Mengyu Hong, Muziying Liu, Fang Zhu, Dan Zhao, Guilai Liu, Tiyun Han, Caiyi Fei, Weihong Zeng, Shi Chen, Qiqin Wu, Bofeng Li, Songquan Wu, Yuhua Shang, Huan Ma, Shoubing Zhou, Shi Xu, Tengchuan Jin
{"title":"FcRn-guided antigen trafficking enhances cancer vaccine efficacy.","authors":"Mengyu Hong, Muziying Liu, Fang Zhu, Dan Zhao, Guilai Liu, Tiyun Han, Caiyi Fei, Weihong Zeng, Shi Chen, Qiqin Wu, Bofeng Li, Songquan Wu, Yuhua Shang, Huan Ma, Shoubing Zhou, Shi Xu, Tengchuan Jin","doi":"10.1007/s00262-024-03888-y","DOIUrl":"10.1007/s00262-024-03888-y","url":null,"abstract":"<p><p>The development of tumor vaccines represents a significant focus within cancer therapeutics research. Nonetheless, the efficiency of antigen presentation in tumor vaccine remains suboptimal. We introduce an innovative mRNA-lipid nanoparticle platform designed to express tumor antigenic epitopes fused with the transmembrane domain and cytoplasmic tail of the neonatal Fc receptor (FcRn). This novel design exploits FcRn trafficking signals to direct the epitope-FcRn fusion toward endolysosomal degradation, thereby generating epitopes capable of eliciting targeted T cell responses and establishing immune memory. The FcRn-directed presentation of epitopes enhances MHC class I and II antigen presentation, thereby robustly inducing CD4<sup>+</sup> and CD8<sup>+</sup> T cell responses, which translates to the inhibition of tumor growth and extension of survival in preclinical mouse models. In summary, the deliberate incorporation of FcRn trafficking signals into vaccine design markedly boosts T cell responses, underscoring the promise of this novel strategy in advancing the efficacy of tumor vaccines.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 2","pages":"54"},"PeriodicalIF":4.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920484","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}
Sophia B Strobel, Devayani Machiraju, Melanie Wiecken, Jasmin Richter, Julian A F Klein, Annemarie Berger, Jessica C Hassel
{"title":"CMV IgG in the blood is not associated with hepatitis but correlates with poor outcomes in immunotherapy treated melanoma patients.","authors":"Sophia B Strobel, Devayani Machiraju, Melanie Wiecken, Jasmin Richter, Julian A F Klein, Annemarie Berger, Jessica C Hassel","doi":"10.1007/s00262-024-03859-3","DOIUrl":"10.1007/s00262-024-03859-3","url":null,"abstract":"<p><p>Cytomegalovirus (CMV) infection or reactivation in immune-compromised individuals can lead to a wide range of severe complications including hepatitis. However, its relation with immune checkpoint inhibitors (ICIs) induced hepatitis (ICI-hepatitis) and tumor responses in advanced melanoma patients remains unclear. Hundred and ninety metastatic cutaneous melanoma patients (mCM) who received ICI treatment, with CMV IgG or IgM information available at baseline, were included in the study (Cohort 1). Clinical characteristics and immune cell count in the blood were retrieved from medical records. In addition, anti-CMV IgG and IgM were measured in pre and on-treatment serum samples from 49 advanced skin cancer patients using ELISA (Cohort 2). In the event of a positive anti-CMV IgM, further analysis with PCR was performed. Univariate and multivariate analysis was used to assess the relationship between CMV IgG or IgM and ICI-hepatitis tumor outcomes. Twenty-one patients (11%) developed hepatitis during ICI treatment (Cohort 1). ICI-hepatitis was significantly associated with disease control rate (DCR; p = 0.017) and longer progression-free survival (PFS; p = 0.008) in mCM patients. Detection of CMV IgG or IgM antibodies were not associated with ICI-hepatitis (p > 0.05). However, increased CMV IgG values at baseline correlated with disease progression (p = 0.047) and shorter PFS (p = 0.081). In addition, increased CMV IgG values were associated with reduced levels of monocytes (p = 0.005), eosinophils (p = 0.062), and neutrophils (p = 0.065) in the blood. In summary, anti-CMV IgG or IgM in the blood may not be associated with ICI-hepatitis, but high anti-CMV IgG at baseline indicates poor outcomes in ICI-treated mCM patients.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 2","pages":"59"},"PeriodicalIF":4.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142919595","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}