Oncoimmunology最新文献

{"title":"Expression of CD39 is associated with T cell exhaustion in ovarian cancer and its blockade reverts T cell dysfunction.","authors":"Marius Witt, Leticia Oliveira-Ferrer, Friedrich Koch-Nolte, Stephan Menzel, Louisa Hell, Tabea Sturmheit, Elisa Seubert, Pauline Weimer, Yi Ding, Minyue Qi, Barbara Schmalfeldt, Carsten Bokemeyer, Walter Fiedler, Jasmin Wellbrock, Franziska Brauneck","doi":"10.1080/2162402X.2024.2346359","DOIUrl":"10.1080/2162402X.2024.2346359","url":null,"abstract":"<p><p>Immune exhaustion is a hallmark of ovarian cancer. Using multiparametric flow cytometry, the study aimed to analyze protein expression of novel immunological targets on CD3⁺ T cells isolated from the peripheral blood (<i>n</i> = 20), malignant ascites (<i>n</i> = 16), and tumor tissue (<i>n</i> = 6) of patients with ovarian cancer (OVCA). The study revealed an increased proportion of effector memory CD8⁺ T cells in OVCA tissue and malignant ascites. An OVCA-characteristic PD-1^high CD8⁺ T cell population was detected, which differed from PD-1^lowCD8⁺ T cells by increased co-expression of TIGIT, CD39, and HLA-DR. In addition, these OVCA-characteristic CD8⁺ T cells showed reduced expression of the transcription factor TCF-1, which may also indicate reduced effector function and memory formation. On the contrary, the transcription factor TOX, which significantly regulates terminal T cell-exhaustion, was found more frequently in these cells. Further protein and gene analysis showed that CD39 and CD73 were also expressed on OVCA tumor cells isolated from solid tumors (<i>n</i> = 14) and malignant ascites (<i>n</i> = 9). In the latter compartment, CD39 and CD73 were also associated with the expression of the \"don't eat me\" molecule CD24 on tumor cells. Additionally, ascites-derived CD24⁺EpCAM⁺ tumor cells showed a higher frequency of CD39⁺ or CD73⁺ cells. Furthermore, CD39 expression was associated with unfavorable clinical parameters. Expression of CD39 on T cells was upregulated through CD3/CD28 stimulation and its blockade by a newly developed nanobody construct resulted in increased proliferation (eFluor), activation (CD25 and CD134), and production of cytotoxic cytokines (IFN-γ, TNF-α, and granzyme-B) of CD8⁺ T cells.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2346359"},"PeriodicalIF":6.5,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140913279","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":"Principles of risk assessment in colon cancer: immunity is key.","authors":"Assia Hijazi, Jérôme Galon","doi":"10.1080/2162402X.2024.2347441","DOIUrl":"10.1080/2162402X.2024.2347441","url":null,"abstract":"<p><p>In clinical practice, the administration of adjuvant chemotherapy (ACT) following tumor surgical resection raises a critical dilemma for stage II colon cancer (CC) patients. The prognostic features used to identify high-risk CC patients rely on the pathological assessment of tumor cells. Currently, these factors are considered for stratifying patients who may benefit from ACT at early CC stages. However, the extent to which these factors predict clinical outcomes (<i>i.e</i>. recurrence, survival) remains highly controversial, also uncertainty persists regarding patients' response to treatment, necessitating further investigation. Therefore, an imperious need is to explore novel biomarkers that can reliably stratify patients at risk, to optimize adjuvant treatment decisions. Recently, we evaluated the prognostic and predictive value of Immunoscore (IS), an immune digital-pathology assay, in stage II CC patients. IS emerged as the sole significant parameter for predicting disease-free survival (DFS) in high-risk patients. Moreover, IS effectively stratified patients who would benefit most from ACT based on their risk of recurrence, thus predicting their outcomes. Notably, our findings revealed that digital IS outperformed the visual quantitative assessment of the immune response conducted by expert pathologists. The latest edition of the WHO classification for digestive tumor has introduced the evaluation of the immune response, as assessed by IS, as desirable and essential diagnostic criterion. This supports the revision of current cancer guidelines and strongly recommends the implementation of IS into clinical practice as a patient stratification tool, to guide CC treatment decisions. This approach may provide appropriate personalized therapeutic decisions that could critically impact early-stage CC patient care.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2347441"},"PeriodicalIF":6.5,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140854219","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":"Immune checkpoint therapy responders display early clonal expansion of tumor infiltrating lymphocytes.","authors":"Joel Kidman, Rachael M Zemek, John-William Sidhom, Debora Correa, Nicola Principe, Fezaan Sheikh, Vanessa S Fear, Catherine A Forbes, Abha Chopra, Louis Boon, Ayham Zaitouny, Emma de Jong, Robert A Holt, Matt Jones, Michael J Millward, Timo Lassmann, Alistair R R Forrest, Anna K Nowak, Mark Watson, Richard A Lake, W Joost Lesterhuis, Jonathan Chee","doi":"10.1080/2162402X.2024.2345859","DOIUrl":"https://doi.org/10.1080/2162402X.2024.2345859","url":null,"abstract":"<p><p>Immune checkpoint therapy (ICT) causes durable tumour responses in a subgroup of patients, but it is not well known how T cell receptor beta (TCRβ) repertoire dynamics contribute to the therapeutic response. Using murine models that exclude variation in host genetics, environmental factors and tumour mutation burden, limiting variation between animals to naturally diverse TCRβ repertoires, we applied TCRseq, single cell RNAseq and flow cytometry to study TCRβ repertoire dynamics in ICT responders and non-responders. Increased oligoclonal expansion of TCRβ clonotypes was observed in responding tumours. Machine learning identified TCRβ CDR3 signatures unique to each tumour model, and signatures associated with ICT response at various timepoints before or during ICT. Clonally expanded CD8+ T cells in responding tumours post ICT displayed effector T cell gene signatures and phenotype. An early burst of clonal expansion during ICT is associated with response, and we report unique dynamics in TCRβ signatures associated with ICT response.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2345859"},"PeriodicalIF":7.2,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11057660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140855601","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":"Co-inhibition of TGF-β and PD-L1 pathways in a metastatic colorectal cancer mouse model triggers interferon responses, innate cells and T cells, alongside metabolic changes and tumor resistance.","authors":"Reshmi Nair, Tamsin R M Lannagan, Rene Jackstadt, Anna Andrusaite, John Cole, Caitlin Boyne, Robert J B Nibbs, Owen J Sansom, Simon Milling","doi":"10.1080/2162402X.2024.2330194","DOIUrl":"10.1080/2162402X.2024.2330194","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is the third most prevalent cancer worldwide with a high mortality rate (20-30%), especially due to metastasis to adjacent organs. Clinical responses to chemotherapy, radiation, targeted and immunotherapies are limited to a subset of patients making metastatic CRC (mCRC) difficult to treat. To understand the therapeutic modulation of immune response in mCRC, we have used a genetically engineered mouse model (GEMM), \"KPN\", which resembles the human 'CMS4'-like subtype. We show here that transforming growth factor (TGF-β1), secreted by KPN organoids, increases cancer cell proliferation, and inhibits splenocyte activation <i>in vitro</i>. TGF-β1 also inhibits activation of naive but not pre-activated T cells, suggesting differential effects on specific immune cells. <i>In vivo</i>, the inhibition of TGF-β inflames the KPN tumors, causing infiltration of T cells, monocytes and monocytic intermediates, while reducing neutrophils and epithelial cells. Co-inhibition of TGF-β and PD-L1 signaling further enhances cytotoxic CD8⁺T cells and upregulates innate immune response and interferon gene signatures. However, simultaneous upregulation of cancer-related metabolic genes correlated with limited control of tumor burden and/or progression despite combination treatment. Our study illustrates the importance of using GEMMs to predict better immunotherapies for mCRC.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2330194"},"PeriodicalIF":7.2,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10956632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140186013","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":"Transmembrane TNF-TNFR2 signaling as a critical immunoregulatory node in pancreatic cancer.","authors":"Erin M Dickey, Anna Bianchi, Haleh Amirian, Peter J Hosein, Denise Faustman, Roberta Brambilla, Jashodeep Datta","doi":"10.1080/2162402X.2024.2326694","DOIUrl":"10.1080/2162402X.2024.2326694","url":null,"abstract":"<p><p>Pancreatic cancer is characterized by extreme therapeutic resistance. In pancreatic cancers harboring high-risk genomes, we describe that cancer cell-neutrophil signaling circuitry provokes neutrophil-derived transmembrane (tm)TNF-TNFR2 interactions that dictate inflammatory polarization in cancer-associated fibroblasts and T-cell dysfunction - two hallmarks of therapeutic resistance. Targeting tmTNF-TNFR2 signaling may sensitize pancreatic cancer to chemo±immunotherapy.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2326694"},"PeriodicalIF":7.2,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10936673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140121117","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":"Are tumor-associated carbohydrates the missing link between the gut microbiome and response to immune checkpoint inhibitor treatment in cancer?","authors":"Zoltan Szallasi, Aurel Prosz, Zsofia Sztupinszki, Judit Moldvay","doi":"10.1080/2162402X.2024.2324493","DOIUrl":"10.1080/2162402X.2024.2324493","url":null,"abstract":"<p><p>Immune checkpoint inhibitor therapy has dramatically improved survival in a significant subset of patients with several solid tumor types. Increasing the number of patients benefitting from this form of therapy is an important translational research goal. Correlations between the composition of the gut microbiome and response to immune checkpoint inhibitor therapy raised the possibility that direct modulation of the gut microbiome may significantly improve the clinical benefit of this treatment. Several lines of observations suggest that tumor-associated carbohydrates, including those recognized as blood group-related glycolipid antigens, such as the Forssman antigen, may be some of the key factors behind this clinical correlation. Such antigens are expressed in human cancer, humans often produce antibodies against those, and they can induce antibody directed cellular cytotoxicity. Importantly, these antibodies are often induced by antigens present in microbes of the gut. If identified, these antibodies could be boosted by appropriate vaccination techniques and thus enhance anti-tumor immunity with minimal side effects.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2324493"},"PeriodicalIF":7.2,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10913702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140040649","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":"Trial watch: bispecific antibodies for the treatment of relapsed or refractory large B-cell lymphoma.","authors":"Giulio Cassanello, Alejandro Luna de Abia, Lorenzo Falchi","doi":"10.1080/2162402X.2024.2321648","DOIUrl":"10.1080/2162402X.2024.2321648","url":null,"abstract":"<p><p>Immunotherapy has shaped the treatment approach to diffuse large B-cell lymphoma (DLBCL), with rituximab leading to remarkable improvements in outcomes for both relapsed and treatment-naïve patients. Recently, groundbreaking immunotherapies like chimeric antigen receptor T-cells have entered the treatment arena for relapsed/refractory (R/R) DLBCL and gained regulatory approval in several countries. The concept of harnessing a patient's own T-cells to combat cancer has been further explored through the development of bispecific antibodies (BsAbs), a class of engineered antibody products designed to simultaneously target two different antigens. These novel drugs have demonstrated impressive single-agent activity and manageable toxicity in patients with heavily pretreated B-cell non-Hodgkin lymphoma. In this review, we provide an up-to-date overview of recently completed or ongoing BsAbs trials in patients with R/R DLBCL, including single-agent results, emerging combination data, and novel constructs.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2321648"},"PeriodicalIF":7.2,"publicationDate":"2024-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10913711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140040650","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":"Noninvasive radiomic biomarkers for predicting pseudoprogression and hyperprogression in patients with non-small cell lung cancer treated with immune checkpoint inhibition.","authors":"Yikun Li, Peiliang Wang, Junhao Xu, Xiaonan Shi, Tianwen Yin, Feifei Teng","doi":"10.1080/2162402X.2024.2312628","DOIUrl":"10.1080/2162402X.2024.2312628","url":null,"abstract":"<p><p>This study aimed to develop a computed tomography (CT)-based radiomics model capable of precisely predicting hyperprogression and pseudoprogression (PP) in patients with non-small cell lung cancer (NSCLC) treated with immunotherapy. We retrospectively analyzed 105 patients with NSCLC, from three institutions, treated with immune checkpoint inhibitors (ICIs) and categorized them into training and independent testing set. Subsequently, we processed CT scans with a series of image-preprocessing techniques, and 6008 radiomic features capturing intra- and peritumoral texture patterns were extracted. We used the least absolute shrinkage and selection operator logistic regression model to select radiomic features and construct machine learning models. To further differentiate between progressive disease (PD) and hyperprogressive disease (HPD), we developed a new radiomics model. The logistic regression (LR) model showed optimal performance in distinguishing PP from HPD, with areas under the receiver operating characteristic curve (AUC) of 0.95 (95% confidence interval [CI]: 0.91-0.99) and 0.88 (95% CI: 0.66-1) in the training and testing sets, respectively. Additionally, the support vector machine model showed optimal performance in distinguishing PD from HPD, with AUC of 0.97 (95% CI: 0.93-1) and 0.87 (95% CI: 0.72-1) in the training and testing sets, respectively. Kaplan‒Meier survival curves showed clear stratification between PP predicted by the radiomics model and true progression (HPD and PD) (hazard ratio = 0.337, 95% CI: 0.200-0.568, <i>p</i> < 0.01) in overall survival. Our study demonstrates that radiomic features extracted from baseline CT scans are effective in predicting PP and HPD in patients with NSCLC treated with ICIs.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2312628"},"PeriodicalIF":7.2,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10857548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139724593","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":"Immune checkpoint blockade improves the activation and function of circulating mucosal-associated invariant T (MAIT) cells in patients with non-small cell lung cancer.","authors":"Patrik Sundström, Nikita Dutta, William Rodin, Andreas Hallqvist, Sukanya Raghavan, Marianne Quiding Järbrink","doi":"10.1080/2162402X.2024.2312631","DOIUrl":"10.1080/2162402X.2024.2312631","url":null,"abstract":"<p><p>Mucosal-associated invariant T (MAIT) cells constitute one of the most numerous unconventional T cell subsets, and are characterized by rapid release of Th1- and Th17-associated cytokines and increased cytotoxic functions following activation. MAIT cells accumulate in tumor tissue but show an exhausted phenotype. Here, we investigated if immune checkpoint blockade (ICB) with antibodies to PD-1 or PD-L1 affects the function of circulating MAIT cells from non-small cell lung cancer patients. ICB increased the proliferation and co-expression of the activation markers HLA-DR and CD38 on MAIT cells in most patients after the first treatment cycle, irrespective of treatment outcome. Furthermore, production of cytokines, especially TNF and IL-2, also increased after treatment, as did MAIT cell polyfunctionality. These results indicate that MAIT cells respond to ICB, and that MAIT cell reinvigoration may contribute to tumor regression in patients undergoing immune checkpoint therapy.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2312631"},"PeriodicalIF":7.2,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10854269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139724592","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":"Platelet-derived microparticles adoptively transfer integrin β3 to promote antitumor effect of tumor-infiltrating T cells.","authors":"Mimi Zhou, Yali Feng, Xiaoli Zhang, Jianguo Chen, Naijuan Yao, Shan Fu, Tianzhi Ni, Yi Chen, Fei Xie, Sahasrabda Roy, Jinfeng Liu, Yuan Yang, Yingli He, Yingren Zhao, Nan Yang","doi":"10.1080/2162402X.2024.2304963","DOIUrl":"10.1080/2162402X.2024.2304963","url":null,"abstract":"<p><p>Approximately two-thirds of hepatocellular carcinoma (HCC) is considered a \"cold tumor\" characterized by few tumor-infiltrating T cells and an abundance of immunosuppressive cells. Cilengitide, an integrin αvβ3 inhibitor, has failed in clinical trials as a potential anticancer drug. This failure implies that integrin αvβ3 may play an important role in immune cells. However, the expression and potential role of integrin αvβ3 in T cells of HCC patients remain unknown. Here, we established two HCC models and found that cilengitide had a dual effect on the HCC microenvironment by exerting both antitumor effect and immunosuppressive effect on T cells. This may partly explain the failure of cilengitide in clinical trials. In clinical specimens, HCC-infiltrating T cells exhibited deficient expression and activation of integrin β3, which was associated with poor T-cell infiltration into tumors. Additionally, integrin β3 functioned as a positive immunomodulatory molecule to facilitate T-cell infiltration and T helper 1-type immune response in vitro. Furthermore, T cells and platelet-derived microparticles (PMPs) co-culture assay revealed that PMPs adoptively transferred integrin β3 to T cells and positively regulated T cell immune response. This process was mediated by clathrin-dependent endocytosis and macropinocytosis. Our data demonstrate that integrin β3 deficiency on HCC-infiltrating T cells may be involved in shaping the immunosuppressive tumor microenvironment. PMPs transfer integrin β3 to T cells and positively regulate T cell immune response, which may provide a new insight into immune therapy of HCC.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2304963"},"PeriodicalIF":7.2,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10793703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139486521","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}