Oncoimmunology最新文献

{"title":"Whole stromal fibroblast signature is linked to specific chemokine and immune infiltration patterns and to improved survival in NSCLC.","authors":"Stefan Koeck, Arno Amann, Johan Kern, Marit Zwierzina, Edith Lorenz, Sieghart Sopper, Heinz Zwierzina, Finn Mildner, Martina Sykora, Susanne Sprung, Hubert Hackl, Florian Augustin, Hubert T Maier, Andreas Pircher, Georg Pall, Dominik Wolf, Gabriele Gamerith","doi":"10.1080/2162402X.2023.2274130","DOIUrl":"https://doi.org/10.1080/2162402X.2023.2274130","url":null,"abstract":"<p><p>Cancer associated fibroblasts (CAF) are known to orchestrate multiple components of the tumor microenvironment, whereas the influence of the whole stromal-fibroblast compartment is less understood. Here, an extended stromal fibroblast signature was investigated to define its impact on immune cell infiltration. The lung cancer adenocarcinoma (LUAD) data set of the cancer genome atlas (TCGA) was used to test whole stroma signatures and cancer-associated fibroblast signatures for their impact on prognosis. 3D cell cultures of the NSCLC cancer cell line A549 together with the fibroblast cell line SV80 were used in combination with infiltrating peripheral blood mononuclear cells (PBMC) for in-vitro investigations. Immune cell infiltration was assessed <i>via</i> flow cytometry, chemokines were analyzed by immunoassays and RNA microarrays. Results were confirmed in specimens from NSCLC patients by flow cytometry or immunohistochemistry as well as in the TCGA data set. The TCGA analyses correlated the whole stromal-fibroblast signature with an improved outcome, whereas no effect was found for the CAF signatures. In 3D microtumors, the presence of fibroblasts induced infiltration of B cells and CD69⁺CD4⁺ T cells, which was linked to an increased expression of CCL13 and CXCL16. The stroma/lymphocyte interaction was confirmed in NSCLC patients, as stroma-rich tumors displayed an elevated B cell count and survival in the local cohort and the TCGA data set. A whole stromal fibroblast signature was associated with an improved clinical outcome in lung adenocarcinoma and in vitro and in vivo experiments suggest that this signature increases B and T cell recruitment <i>via</i> induction of chemokines.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"12 1","pages":"2274130"},"PeriodicalIF":7.2,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10732611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138832494","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":"Emergence of immune-related adverse events correlates with pathological complete response in patients receiving pembrolizumab for early triple-negative breast cancer","authors":"Maximilian Marhold, Simon Udovica, Anna Halstead, Mona Hirdler, Muna Ferner, Kerstin Wimmer, Zsuzsanna Bago-Horvath, Ruth Exner, Florian Fitzal, Kathrin Strasser-Weippl, Tim Robinson, Rupert Bartsch","doi":"10.1080/2162402x.2023.2275846","DOIUrl":"https://doi.org/10.1080/2162402x.2023.2275846","url":null,"abstract":"Based upon results of the KEYNOTE-522 trial and following approval by regulatory authorities, the addition of pembrolizumab to chemotherapy is now the standard-of-care for the treatment of early triple-negative breast cancer (eTNBC) (Clinical stage II-III). Pembrolizumab is a programmed cell death protein 1 monoclonal antibody, known to cause immune-related adverse events (irAEs) in a significant subset of patients. Real-world data on incidence, type and treatment strategies of irAEs in the setting of eTNBC treatment are sparse. In this multicenterretrospective analysis, we characterized real-world incidence of irAEs and treatment outcomes such as pathological complete response (pCR) from the combination of pembrolizumab and chemotherapy as neoadjuvant treatment for eTNBC.","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"51 13","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136348447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunogenic chemotherapy sensitizes RAS-mutated colorectal cancers to immune checkpoint inhibitors","authors":"Lucillia Bezu, Oliver Kepp, Guido Kroemer","doi":"10.1080/2162402x.2023.2272352","DOIUrl":"https://doi.org/10.1080/2162402x.2023.2272352","url":null,"abstract":"Recent clinical trials have compared the use of different chemotherapeutic regimens as “immune induction therapies” to sensitize cancers to immune checkpoint inhibitors (ICI). Cytotoxic drugs reputed to be inducers of immunogenic cell death (ICD) appeared to be particularly efficient for this purpose. A trial published in Nature Medicine by Thibaudin et al. reveals the capacity of oxaliplatin-based chemotherapy to sensitize RAS-mutant unresectable metastatic colorectal cancer to ICIs blocking CTLA-4 and PD-L1.","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":" 19","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135290520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Next-generation CTLA-4 targeting molecules and combination therapy: promising strategies for improving cancer immunotherapy.","authors":"Nils-Petter Rudqvist, Manushak Avagyan, Dhan Chand","doi":"10.1080/2162402X.2023.2275333","DOIUrl":"10.1080/2162402X.2023.2275333","url":null,"abstract":"<p><p>Radiation therapy and anti-CTLA-4 combination therapy can induce meaningful responses in some patients. Adding CD40 may provide additional benefit. Next-generation anti-CTLA-4 antibodies, such as botensilimab, are showing promise in clinical trials. Combining botensilimab with RT and/or CD40 agonist may offer additional benefits for challenging tumor types.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"12 1","pages":"2275333"},"PeriodicalIF":7.2,"publicationDate":"2023-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10627057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71491221","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":"Interleukin-27 tackles immunosuppression in chronic lymphocytic leukemia.","authors":"Iria Fernandez Botana, Giulia Pagano, Etienne Moussay, Jerome Paggetti","doi":"10.1080/2162402X.2023.2276490","DOIUrl":"10.1080/2162402X.2023.2276490","url":null,"abstract":"<p><p>Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the western world. It is characterized by a high dependency on interactions with the surrounding immune landscape, highlighting its suitability for immune-mediated therapeutic interventions. We recently revealed that the cytokine IL-27 exerts a strong anti-tumor role in CLL through a T-cell-mediated mechanism.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"12 1","pages":"2276490"},"PeriodicalIF":7.2,"publicationDate":"2023-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10627055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71491220","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":"Safety and effectiveness of combination versus monotherapy with immune checkpoint inhibitors in patients with preexisting autoimmune diseases","authors":"Pankti Reid, Sabina Sandigursky, Juhee Song, Maria A. Lopez-Olivo, Houssein Safa, Samuel Cytryn, Elizaveta Efuni, Maryam Buni, Anna Pavlick, Michelle Krogsgaard, Osama Abu-Shawer, Mehmet Altan, Jeffrey S. Weber, Osama E. Rahma, Maria E. Suarez-Almazor, Adi Diab, Noha Abdel-Wahab","doi":"10.1080/2162402x.2023.2261264","DOIUrl":"https://doi.org/10.1080/2162402x.2023.2261264","url":null,"abstract":"","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"38 10","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136104683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Driver mutations in <i>GNAQ</i> and <i>GNA11</i> genes as potential targets for precision immunotherapy in uveal melanoma patients","authors":"Sandra García-Mulero, Roberto Fornelino, Marco Punta, Stefano Lise, Mar Varela, Luis P. del Carpio, Rafael Moreno, Marcel Costa-García, Dietmar Rieder, Zlatko Trajanoski, Alena Gros, Ramón Alemany, Josep María Piulats, Rebeca Sanz-Pamplona","doi":"10.1080/2162402x.2023.2261278","DOIUrl":"https://doi.org/10.1080/2162402x.2023.2261278","url":null,"abstract":"Uveal melanoma (UM) is the most common ocular malignancy in adults. Nearly 95% of UM patients carry the mutually exclusive mutations in the homologous genes GNAQ (amino acid change Q209L/Q209P) and GNA11 (aminoacid change Q209L). UM is located in an immunosuppressed organ and does not suffer immunoediting. Therefore, we hypothesize that driver mutations in GNAQ/11 genes could be recognized by the immune system. Genomic and transcriptomic data from primary uveal tumors were collected from the TCGA-UM dataset (n = 80) and used to assess the immunogenic potential for GNAQ/GNA11 Q209L/Q209P mutations using a variety of tools and HLA type information. All prediction tools showed stronger GNAQ/11 Q209L binding to HLA than GNAQ/11 Q209P. The immunogenicity analysis revealed that Q209L is likely to be presented by more than 73% of individuals in 1000 G databases whereas Q209P is only predicted to be presented in 24% of individuals. GNAQ/11 Q209L showed a higher likelihood to be presented by HLA-I molecules than almost all driver mutations analyzed. Finally, samples carrying Q209L had a higher immune-reactive phenotype. Regarding cancer risk, seven HLA genotypes with low Q209L affinity show higher frequency in uveal melanoma patients than in the general population. However, no clear association was found between any HLA genotype and survival. Results suggest a high potential immunogenicity of the GNAQ/11 Q209L variant that could allow the generation of novel therapeutic tools to treat UM like neoantigen vaccinations.","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 3","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135273398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial heterogeneity of T cell repertoire across NSCLC tumors, tumor edges, adjacent and distant lung tissues.","authors":"Qikang Hu,&nbsp;Meredith L Frank,&nbsp;Yang Gao,&nbsp;Liyan Ji,&nbsp;Muyun Peng,&nbsp;Chen Chen,&nbsp;Bin Wang,&nbsp;Yan Hu,&nbsp;Zeyu Wu,&nbsp;Jina Li,&nbsp;Lu Shu,&nbsp;Qiongzhi He,&nbsp;Yingqian Zhang,&nbsp;Xuefeng Xia,&nbsp;Jianjun Zhang,&nbsp;Xin Yi,&nbsp;Alexandre Reuben,&nbsp;Fenglei Yu","doi":"10.1080/2162402X.2023.2233399","DOIUrl":"10.1080/2162402X.2023.2233399","url":null,"abstract":"<p><strong>Background: </strong>A better understanding of T cells in lung cancer and their distribution across tumor-adjacent lungs and peripheral blood is needed to improve efficacy and minimize toxicity from immunotherapy to lung cancer patients.</p><p><strong>Methods: </strong>Here, we performed CDR3β TCR sequencing of 136 samples from 20 patients with early-stage NSCLC including peripheral blood mononuclear cells, tumors, tumor edges (<1 cm from tumor), as well as adjacent lungs 1 cm, 2 cm, 5 cm, and 10 cm away from the tumor to gain insight into the spatial heterogeneity of T cells across the lungs in patients with NSCLC. PD-L1, CD4, and CD8 expression was assessed using immunohistochemical staining, and genomic features were derived by targeted sequencing of 1,021 cancer-related genes. Multiplex immunohistochemistry against PD-1, CTLA4, LAG3, and TIM3 was performed on four patients to assess T cell exhaustion.</p><p><strong>Results: </strong>Our study reveals a decreasing gradient in TIL Tumor Infiltrating Lymphocytes homology with tumor edge, adjacent lungs, and peripheral blood but no discernible distance-associated patterns of T cell trafficking within the adjacent lung itself. Furthermore, we show a decrease in pathogen-specific TCRs in regions with high T cell clonality and PD-L1 expression.</p><p><strong>Conclusions: </strong>Exclusion in T exhaustion cells at play across the lungs of patients with NSCLC may potentially be the mechanism for lung cancer occurrence.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"12 1","pages":"2233399"},"PeriodicalIF":7.2,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e2/b0/KONI_12_2233399.PMC10591778.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50159071","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":"CD4+ T cell-derived IL-22 enhances liver metastasis by promoting angiogenesis.","authors":"Tao Zhang, Ramez Wahib, Dimitra E Zazara, Jöran Lücke, Ahmad Mustafa Shiri, Jan Kempski, Lilan Zhao, Theodora Agalioti, Andres Pablo Machicote, Olympia Giannou, Ioannis Belios, Rongrong Jia, Siwen Zhang, Joseph Tintelnot, Hannes Seese, Julia Kristin Grass, Baris Mercanoglu, Louisa Stern, Pasquale Scognamiglio, Mohammad Fard-Aghaie, Philipp Seeger, Jonas Wakker, Marius Kemper, Benjamin Brunswig, Anna Duprée, Panagis M Lykoudis, Anastasia Pikouli, Emmanouil Giorgakis, Pablo Stringa, Natalia Lausada, Maria Virginia Gentilini, Gabriel E Gondolesi, Kai Bachmann, Philipp Busch, Rainer Grotelüschen, Ioannis C Maroulis, Petra C Arck, Ryosuke Nakano, Angus W Thomson, Tarik Ghadban, Michael Tachezy, Nathaniel Melling, Eike-Gert Achilles, Victor G Puelles, Felix Nickel, Thilo Hackert, Oliver Mann, Jakob R Izbicki, Jun Li, Nicola Gagliani, Samuel Huber, Anastasios D Giannou","doi":"10.1080/2162402X.2023.2269634","DOIUrl":"10.1080/2162402X.2023.2269634","url":null,"abstract":"<p><p>Metastasis is a cancer-related systemic disease and is responsible for the greatest mortality rate among cancer patients. Interestingly, the interaction between the immune system and cancer cells seems to play a key role in metastasis formation in the target organ. However, this complex network is only partially understood. We previously found that IL-22 produced by tissue resident iNKT17 cells promotes cancer cell extravasation, the early step of metastasis. Based on these data, we aimed here to decipher the role of IL-22 in the last step of metastasis formation. We found that IL-22 levels were increased in established metastatic sites in both human and mouse. We also found that Th22 cells were the key source of IL-22 in established metastasis sites, and that deletion of IL-22 in CD4+ T cells was protective in liver metastasis formation. Accordingly, the administration of a murine IL-22 neutralizing antibody in the establishment of metastasis formation significantly reduced the metastatic burden in a mouse model. Mechanistically, IL-22-producing Th22 cells promoted angiogenesis in established metastasis sites. In conclusion, our findings highlight that IL-22 is equally as important in contributing to metastasis formation at late metastatic stages, and thus, identify it as a novel therapeutic target in established metastasis.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"12 1","pages":"2269634"},"PeriodicalIF":7.2,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2e/86/KONI_12_2269634.PMC10591777.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50159070","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":"<i>PD-L1</i> (<i>CD274</i>) promoter hypomethylation predicts immunotherapy response in metastatic urothelial carcinoma.","authors":"Niklas Klümper, Lennert Wüst, Jonas Saal, Damian J Ralser, Romina Zarbl, Jonas Jarczyk, Johannes Breyer, Danijel Sikic, Bernd Wullich, Christian Bolenz, Florian Roghmann, Michael Hölzel, Manuel Ritter, Sebastian Strieth, Arndt Hartmann, Philipp Erben, Ralph M Wirtz, Jennifer Landsberg, Dimo Dietrich, Markus Eckstein","doi":"10.1080/2162402X.2023.2267744","DOIUrl":"10.1080/2162402X.2023.2267744","url":null,"abstract":"<p><p>PD-L1 status assessed by immunohistochemistry (IHC) has failed to reliably predict outcomes for patients with metastatic urothelial carcinoma (mUC) on immune checkpoint blockade (ICB). <i>PD-L1</i> promoter methylation is an epigenetic mechanism that has been shown to regulate <i>PD-L1</i> mRNA expression in various malignancies. The aim of our present study was to evaluate the predictive potential of <i>PD-L1</i> promoter methylation status (<i>mPD-L1</i>) in ICB-treated mUC compared to conventional IHC-based PD-L1 assessment. We quantified <i>mPD-L1</i> in formalin-fixed and paraffin-embedded tissue sections using an established quantitative methylation-specific PCR assay (qMSP) in a well-characterized multicenter ICB-treated cohort comprising <i>N</i> = 107 patients with mUC. Additionally, PD-L1 protein expression in tumor tissues was assessed using regulatory approved IHC protocols. The effect of pharmacological hypomethylation by the DNA methyltransferase inhibitor decitabine in combination with interferon-γ stimulation in urothelial carcinoma cell lines was investigated by IHC and FACS. <i>mPD-L1</i> hypomethylation predicted objective response rate at the first staging on ICB. Patients with tumors categorized as <i>PD-L1</i> hypomethylated (lower quartile) showed significantly prolonged progression-free (PFS) and overall survival (OS) after ICB initiation. In contrast, PD-L1 protein expression status neither correlated with response nor survival. In multivariable Cox regression analyses, <i>PD-L1</i> promoter hypermethylation remained an independent predictor of unfavorable PFS and OS. In urothelial carcinoma cell lines, pharmacological demethylation led to an upregulation of membranous PD-L1 expression and an enhanced inducibility of PD-L1 expression by interferon γ. Hypomethylation of the <i>PD-L1</i> promoter is a promising predictive biomarker for response to ICB in patients with mUC.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"12 1","pages":"2267744"},"PeriodicalIF":7.2,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/60/52/KONI_12_2267744.PMC10588513.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49693160","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}