Oncoimmunology最新文献

{"title":"<i>Faecalibaterium prausnitzii</i> strain EXL01 boosts efficacy of immune checkpoint inhibitors.","authors":"Marius Bredon, Camille Danne, Hang Phuong Pham, Pauline Ruffié, Alban Bessede, Nathalie Rolhion, Laura Creusot, Loic Brot, Iria Alonso, Philippe Langella, Lisa Derosa, Alexis B Cortot, Bertrand Routy, Laurence Zitvogel, Nicola Segata, Harry Sokol","doi":"10.1080/2162402X.2024.2374954","DOIUrl":"10.1080/2162402X.2024.2374954","url":null,"abstract":"<p><p>Gut microbiota impacts responses to immune checkpoint inhibitors (ICI). A high level of <i>Faecalibacterium prausnitzii</i> have been associated with a positive response to ICI in multiple cancer types. Here, based on fecal shotgun metagenomics data, we show in two independent cohorts of patients with non-small cell lung cancer and advanced melanoma that a high level of <i>F. prausnitzii</i> at baseline is positively associated with a better clinical response to ICI. In MCA205 tumor-bearing mice, administration of <i>F.</i> <i>prausnitzii</i> strain EXL01, already in clinical development for Inflammatory Bowel Disease, restores the anti-tumor response to ICI in the context of antibiotic-induced microbiota perturbation at clinical and tumor transcriptomics level. In vitro, EXL01 strain enhances T cell activation in the presence of ICI. Interestingly, oral administration of EXL01 strain did not induce any change in fecal microbiota diversity or composition, suggesting a direct effect on immune cells in the small intestine. <i>F. prausnitzii</i> strain EXL01 will be evaluated as an adjuvant to ICI in multiple cancers in the near future.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2374954"},"PeriodicalIF":6.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11218805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141493992","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":"Complete response of metastatic microsatellite-stable <i>BRAF</i> V600E colorectal cancer to first-line oxaliplatin-based chemotherapy and immune checkpoint blockade.","authors":"Anne Hansen Ree, Eirik Høye, Ying Esbensen, Ann-Christin R Beitnes, Anne Negård, Linn Bernklev, Linn Kruse Tetlie, Åsmund A Fretland, Hanne M Hamre, Christian Kersten, Eva Hofsli, Marianne G Guren, Halfdan Sorbye, Hilde L Nilsen, Kjersti Flatmark, Sebastian Meltzer","doi":"10.1080/2162402X.2024.2372886","DOIUrl":"10.1080/2162402X.2024.2372886","url":null,"abstract":"<p><p>The randomized METIMMOX trial (NCT03388190) examined if patients with previously untreated, unresectable abdominal metastases from microsatellite-stable (MSS) colorectal cancer (CRC) might benefit from potentially immunogenic, short-course oxaliplatin-based chemotherapy alternating with immune checkpoint blockade (ICB). Three of 38 patients assigned to this experimental treatment had metastases from <i>BRAF</i>-mutant MSS-CRC, in general a poor-prognostic subgroup explored here. The ≥70-year-old females presented with ascending colon adenocarcinomas with intermediate tumor mutational burden (6.2-11.8 mutations per megabase). All experienced early disappearance of the primary tumor followed by complete response of all overt metastatic disease, resulting in progression-free survival as long as 20-35 months. However, they encountered recurrence at previously unaffected sites and ultimately sanctuary organs, or as intrahepatic tumor evolution reflected in the terminal loss of initially induced T-cell clonality in liver metastases. Yet, the remarkable first-line responses to short-course oxaliplatin-based chemotherapy alternating with ICB may offer a novel therapeutic option to a particularly hard-to-treat MSS-CRC subgroup.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2372886"},"PeriodicalIF":6.5,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11216098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477757","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":"Candidate tumor-specific CD8⁺ T cell subsets identified in the malignant pleural effusion of advanced lung cancer patients by single-cell analysis.","authors":"Yusuke Sugita, Daisuke Muraoka, Ayako Demachi-Okamura, Hiroyasu Komuro, Katsuhiro Masago, Eiichi Sasaki, Yasunori Fukushima, Takuya Matsui, Shuichi Shinohara, Yusuke Takahashi, Reina Nishida, Chieko Takashima, Teppei Yamaguchi, Yoshitsugu Horio, Kana Hashimoto, Ichidai Tanaka, Hiroshi Hamana, Hiroyuki Kishi, Daiki Miura, Yuki Tanaka, Kousuke Onoue, Kazuhide Onoguchi, Yoshiko Yamashita, Richard Stratford, Trevor Clancy, Rui Yamaguchi, Hiroaki Kuroda, Hironori Ishibashi, Kenichi Okubo, Hirokazu Matsushita","doi":"10.1080/2162402X.2024.2371556","DOIUrl":"10.1080/2162402X.2024.2371556","url":null,"abstract":"<p><p>Isolation of tumor-specific T cells and their antigen receptors (TCRs) from malignant pleural effusions (MPE) may facilitate the development of TCR-transduced adoptive cellular immunotherapy products for advanced lung cancer patients. However, the characteristics and markers of tumor-specific T-cells in MPE are largely undefined. To this end, to establish the phenotypes and antigen specificities of CD8⁺ T cells, we performed single-cell RNA and TCR sequencing of samples from three advanced lung cancer patients. Dimensionality reduction on a total of 4,983 CD8⁺ T cells revealed 10 clusters including naïve, memory, and exhausted phenotypes. We focused particularly on exhausted T cell clusters and tested their TCR reactivity against neoantigens predicted from autologous cancer cell lines. Four different TCRs specific for the same neoantigen and one orphan TCR specific for the autologous cell line were identified from one of the patients. Differential gene expression analysis in tumor-specific T cells relative to the other T cells identified <i>CXCL13</i>, as a candidate gene expressed by tumor-specific T cells. In addition to expressing <i>CXCL13</i>, tumor-specific T cells were present in a higher proportion of T cells co-expressing <i>PDCD1</i>(PD-1)/<i>TNFRSF9</i>(4-1BB). Furthermore, flow cytometric analyses in advanced lung cancer patients with MPE documented that those with high PD-1/4-1BB expression have a better prognosis in the subset of 57 adenocarcinoma patients (<i>p</i> = .039). These data suggest that PD-1/4-1BB co-expression might identify tumor-specific CD8⁺ T cells in MPE, which are associated with patients' prognosis. (233 words).</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2371556"},"PeriodicalIF":6.5,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11216099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477755","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":"Novel mRNA adjuvant ImmunER enhances prostate cancer tumor-associated antigen mRNA therapy via augmenting T cell activity.","authors":"Zhen Xu, Ze-Xiu Xiao, Jing Wang, Hao-Wei Qiu, Fei Cao, Shi-Qiang Zhang, Yuan-Dong Xu, Han-Qi Lei, Heng Xia, Yun-Ru He, Gao-Feng Zha, Jun Pang","doi":"10.1080/2162402X.2024.2373526","DOIUrl":"10.1080/2162402X.2024.2373526","url":null,"abstract":"<p><p>Prostate cancer (PCa) is characterized as a \"cold tumor\" with limited immune responses, rendering the tumor resistant to immune checkpoint inhibitors (ICI). Therapeutic messenger RNA (mRNA) vaccines have emerged as a promising strategy to overcome this challenge by enhancing immune reactivity and significantly boosting anti-tumor efficacy. In our study, we synthesized Tetra, an mRNA vaccine mixed with multiple tumor-associated antigens, and ImmunER, an immune-enhancing adjuvant, aiming to induce potent anti-tumor immunity. ImmunER exhibited the capacity to promote dendritic cells (DCs) maturation, enhance DCs migration, and improve antigen presentation at both cellular and animal levels. Moreover, Tetra, in combination with ImmunER, induced a transformation of bone marrow-derived dendritic cells (BMDCs) to cDC1-CCL22 and up-regulated the JAK-STAT1 pathway, promoting the release of IL-12, TNF-α, and other cytokines. This cascade led to enhanced proliferation and activation of T cells, resulting in effective killing of tumor cells. In vivo experiments further revealed that Tetra + ImmunER increased CD8⁺T cell infiltration and activation in RM-1-PSMA tumor tissues. In summary, our findings underscore the promising potential of the integrated Tetra and ImmunER mRNA-LNP therapy for robust anti-tumor immunity in PCa.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2373526"},"PeriodicalIF":6.5,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11212567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471773","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":"CD161⁺CD127⁺CD8⁺ T cell subsets can predict the efficacy of anti-PD-1 immunotherapy in non-small cell lung cancer with diabetes mellitus.","authors":"Jingjing Qu, Yuekang Li, Binggen Wu, Qian Shen, Lijun Chen, Wenjia Sun, Bo Wang, Lixiong Ying, Li Wu, Hong Zhou, Jianya Zhou, Jianying Zhou","doi":"10.1080/2162402X.2024.2371575","DOIUrl":"10.1080/2162402X.2024.2371575","url":null,"abstract":"<p><p>The role of CD161⁺CD127⁺CD8⁺ T cells in non-small cell lung cancer (NSCLC) patients with diabetes remains unexplored. This study determined the prevalence, phenotype, and function of CD8⁺ T cell subsets in NSCLC with diabetes. We recruited NSCLC patients (<i>n</i> = 436) treated with anti-PD-1 immunotherapy as first-line treatment. The progression-free survival (PFS), overall survival (OS), T cells infiltration, and peripheral blood immunological characteristics were analyzed in NSCLC patients with or without diabetes. NSCLC patients with diabetes exhibited shorter PFS and OS (<i>p</i> = 0.0069 and <i>p</i> = 0.012, respectively) and significantly lower CD8⁺ T cells infiltration. Mass cytometry by time-of-flight (CyTOF) showed a higher percentage of CD161⁺CD127⁺CD8⁺ T cells among CD8⁺T cells in NSCLC with diabetes before anti-PD-1 treatment (<i>p</i> = 0.0071) than that in NSCLC without diabetes and this trend continued after anti-PD-1 treatment (<i>p</i> = 0.0393). Flow cytometry and multiple-immunofluorescence confirmed that NSCLC with diabetes had significantly higher CD161⁺CD127⁺CD8⁺ T cells to CD8⁺T cells ratios than NSCLC patients without diabetes. The RNA-sequencing analysis revealed immune-cytotoxic genes were reduced in the CD161⁺CD127⁺CD8⁺ T cell subset compared to CD161⁺CD127^-CD8⁺ T cells in NSCLC with diabetes. CD161⁺CD127⁺CD8⁺ T cells exhibited more T cell-exhausted phenotypes in NSCLC with diabetes. NSCLC patients with diabetes with ≥ 6.3% CD161⁺CD127⁺CD8⁺ T cells to CD8⁺T cells ratios showed worse PFS. These findings indicate that diabetes is a risk factor for NSCLC patients who undergo anti-PD-1 immunotherapy.CD161⁺CD127⁺CD8⁺ T cells could be a key indicator of a poor prognosis in NSCLC with diabetes. Our findings would help in advancing anti-PD-1 therapy in NSCLC patients with diabetes.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2371575"},"PeriodicalIF":6.5,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11216103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477756","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":"Identification of RNA-binding protein hnRNP C targeting the 3'UTR of the TAP-associated glycoprotein tapasin in melanoma.","authors":"Yuan Wang, Barbara Seliger","doi":"10.1080/2162402X.2024.2370928","DOIUrl":"10.1080/2162402X.2024.2370928","url":null,"abstract":"<p><p>Deregulation or loss of the human leukocyte antigen class I (HLA-I) molecules on tumor cells leading to inhibition of CD8⁺ T cell recognition is an important tumor immune escape strategy, which could be caused by a posttranscriptional control of molecules in the HLA-I pathway mediated by RNA-binding proteins (RBPs). So far, there exists only limited information about the interaction of RBPs with HLA-I-associated molecules, but own work demonstrated a binding of the heterogeneous ribonucleoprotein C (hnRNP C) to the 3' untranslated region (UTR) of the TAP-associated glycoprotein tapasin (tpn). In this study, <i>in silico</i> analysis of pan-cancer TCGA datasets revealed that hnRNP C is higher expressed in tumor specimens compared to corresponding normal tissues, which is negatively correlated to tpn expression, T cell infiltration and the overall survival of tumor patients. Functional analysis demonstrated an upregulation of tpn expression upon siRNA-mediated downregulation of hnRNP C, which is accompanied by an increased HLA-I surface expression. Thus, hnRNP C has been identified to target tpn and its inhibition could improve the HLA-I surface expression on melanoma cells suggesting its use as a possible biomarker for T-cell-based tumor immunotherapies.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2370928"},"PeriodicalIF":6.5,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11212565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471771","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":"Modulation of blood T cell polyfunctionality and HVEM/BTLA expression are critical determinants of clinical outcome in anti-PD1-treated metastatic melanoma patients.","authors":"Stéphane Dalle, Estelle Verronese, Axelle N'Kodia, Christine Bardin, Céline Rodriguez, Thibault Andrieu, Anais Eberhardt, Gabriel Chemin, Uzma Hasan, Myrtille Le-Bouar, Julie Caramel, Mona Amini-Adle, Nathalie Bendriss-Vermare, Bertrand Dubois, Christophe Caux, Christine Ménétrier-Caux","doi":"10.1080/2162402X.2024.2372118","DOIUrl":"10.1080/2162402X.2024.2372118","url":null,"abstract":"<p><p>The need for reliable biomarkers to predict clinical benefit from anti-PD1 treatment in metastatic melanoma (MM) patients remains unmet. Several parameters have been considered in the tumor environment or the blood, but none has yet achieved sufficient accuracy for routine clinical practice. Whole blood samples from MM patients receiving second-line anti-PD1 treatment (NCT02626065), collected longitudinally, were analyzed by flow cytometry to assess the immune cell subsets absolute numbers, the expression of immune checkpoints or ligands on T cells and the functionality of innate immune cells and T cells. Clinical response was assessed according to Progression-Free Survival (PFS) status at one-year following initiation of anti-PD1 (responders: PFS > 1 year; non-responders: PFS ≤ 1 year). At baseline, several phenotypic and functional alterations in blood immune cells were observed in MM patients compared to healthy donors, but only the proportion of polyfunctional memory CD4+ T cells was associated with response to anti-PD1. Under treatment, a decreased frequency of HVEM on CD4+ and CD8+ T cells after 3 months of treatment identified responding patients, whereas its receptor BTLA was not modulated. Both reduced proportion of CD69-expressing CD4+ and CD8+ T cells and increased number of polyfunctional blood memory T cells after 3 months of treatment were associated with response to anti-PD1. Of upmost importance, the combination of changes of all these markers accurately discriminated between responding and non-responding patients. These results suggest that drugs targeting HVEM/BTLA pathway may be of interest to improve anti-PD1 efficacy.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2372118"},"PeriodicalIF":6.5,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11210932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471772","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":"A phase 2 study of spartalizumab (PDR001) among patients with recurrent or metastatic esophageal squamous cell carcinoma (KCSG HN18-17, K-MASTER project 12).","authors":"Dong Ki Lee, Sook Ryun Park, Yeul Hong Kim, Yun-Gyoo Lee, Su-Jin Shin, Beung-Chul Ahn, Sung Sook Lee, Sun Min Lim, Hye Ryun Kim, Byoung Chul Cho, Min Hee Hong","doi":"10.1080/2162402X.2024.2371563","DOIUrl":"10.1080/2162402X.2024.2371563","url":null,"abstract":"<p><p>Spartalizumab (PDR001) is a humanized IgG4 monoclonal antibody targeting programmed cell death protein 1 (PD-1). We conducted a single-arm, phase 2 trial to investigate the efficacy and safety of spartalizumab in patients with refractory esophageal squamous cell carcinoma (ESCC). Patients with histologically confirmed ESCC who experienced disease progression after platinum-based chemotherapy received 300 mg of intravenous spartalizumab every three weeks until disease progression or occurrence of unacceptable toxicity. The primary endpoint was centrally assessed objective response according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Adverse events were closely monitored throughout the study. From March 2020 through April 2021, 44 patients with ESCC were enrolled. Of the 44 patients, the objective response rate was 20.5% (95% confidence interval: 8.5-32.4). With a median follow-up of 10.9 months, median progression-free survival and overall survival were 3.2 months and 11.2 months, respectively. In addition, the median duration of response was 24.7 months. The most common grade 3 or 4 adverse event was grade 3 dysphagia (eight [18%] patients). Biomarker analyses explored programmed cell death ligand 1 and CD20 as potential predictive markers for PD-1 blockade. Spartalizumab showed promising activity with a manageable safety profile, indicating its potential as a new treatment option for patients with refractory ESCC.</p><p><strong>Trial registration: </strong>The trial was registered at ClinicalTrials.gov under the identifier NCT03785496.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2371563"},"PeriodicalIF":6.5,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11197908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141451984","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":"Loss of β2-integrin function results in metabolic reprogramming of dendritic cells, leading to increased dendritic cell functionality and anti-tumor responses.","authors":"Heidi Harjunpää, Riku Somermäki, Guillem Saldo Rubio, Manlio Fusciello, Sara Feola, Imrul Faisal, Anni I Nieminen, Liang Wang, Marc Llort Asens, Hongxia Zhao, Ove Eriksson, Vincenzo Cerullo, Susanna C Fagerholm","doi":"10.1080/2162402X.2024.2369373","DOIUrl":"10.1080/2162402X.2024.2369373","url":null,"abstract":"<p><p>Dendritic cells (DCs) are the main antigen presenting cells of the immune system and are essential for anti-tumor responses. DC-based immunotherapies are used in cancer treatment, but their functionality is not optimized and their clinical efficacy is currently limited. Approaches to improve DC functionality in anti-tumor immunity are therefore required. We have previously shown that the loss of β2-integrin-mediated adhesion leads to epigenetic reprogramming of bone marrow-derived DCs (BM-DCs), resulting in an increased expression of costimulatory markers (CD86, CD80, and CD40), cytokines (IL-12) and the chemokine receptor CCR7. We now show that the loss of β2-integrin-mediated adhesion of BM-DCs also leads to a generally suppressed metabolic profile, with reduced metabolic rate, decreased ROS production, and lowered glucose uptake in cells. The mRNA levels of glycolytic enzymes and glucose transporters were reduced, indicating transcriptional regulation of the metabolic phenotype. Surprisingly, although signaling through a central regulator of immune cell metabolisms, the mechanistic target of rapamycin (mTOR), was increased in BM-DCs with dysfunctional integrins, rapamycin treatment revealed that mTOR signaling was not involved in suppressing DC metabolism. Instead, bioinformatics and functional analyses showed that the Ikaros transcription factor may be involved in regulating the metabolic profile of non-adhesive DCs. Inversely, we found that induction of metabolic stress through treatment of cells with low levels of an inhibitor of glycolysis, 2-deoxyglucose (2DG), led to increased BM-DC activation. Specifically, 2DG treatment led to increased levels of <i>Il-12</i> and <i>Ccr7</i> mRNA, increased production of IL-12, increased levels of cell surface CCR7 and increased <i>in vitro</i> migration and T cell activation potential. Furthermore, 2DG treatment led to increased histone methylation in cells (H3K4me3, H3K27me3), indicating metabolic reprogramming. Finally, metabolic stress induced by 2DG treatment led to improved BM-DC-mediated anti-tumor responses <i>in vivo</i> in a melanoma cancer model, B16-OVA. In conclusion, our results indicate a role for β2-integrin-mediated adhesion in regulating a novel type of metabolic reprogramming of DCs and DC-mediated anti-tumor responses, which may be targeted to enhance DC-mediated anti-tumor responses in cancer immunotherapy.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2369373"},"PeriodicalIF":6.5,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11195491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141447327","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":"ADA/CD26 axis increases intra-tumor PD-1⁺CD28⁺CD8⁺ T-cell fitness and affects NSCLC prognosis and response to ICB.","authors":"Ornella Franzese, Belinda Palermo, Giuseppe Frisullo, Mariangela Panetta, Giulia Campo, Daniel D'Andrea, Isabella Sperduti, Riccardo Taje, Paolo Visca, Paola Nisticò","doi":"10.1080/2162402X.2024.2371051","DOIUrl":"10.1080/2162402X.2024.2371051","url":null,"abstract":"<p><p>Improving cancer immunotherapy efficacy hinges on identifying key T-cell populations critical for tumor control and response to Immune Checkpoint Blockade (ICB). We have recently reported that while the co-expression of PD-1 and CD28 is associated with impaired functionality in peripheral blood, it significantly enhances T-cell fitness in the tumor site of non-small cell lung cancer (NSCLC) patients. To uncover the underlying mechanisms, we explored the role of CD26, a key player in T-cell activation through its interaction with adenosine deaminase (ADA), a crucial intra/extracellular enzyme able to neutralize local adenosine (ADO). We found that an autocrine ADA/CD26 axis enhances CD8⁺PD-1⁺CD28⁺ T-cell function, particularly within an immunosuppressive environment marked by CD39 expression. Then, we interrogated the TCGA and OAK datasets to gain insight into the prognostic/predictive potential of our findings. We identified a signature predicting overall survival (OS) in LUAD patients and response to atezolizumab in advanced LUAD cases. These findings suggest promising avenues for therapeutic intervention targeting the ADA/CD26 axis.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2371051"},"PeriodicalIF":6.5,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11195478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141447326","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}