Cancer immunology, immunotherapy : CII最新文献

{"title":"Sharpening up tumor microenvironment to enhance the efficacy of immune checkpoint blockade on head and neck cancer using a CpG-oligodeoxynucleotide.","authors":"Jen-Chih Tseng,&nbsp;Jing-Xing Yang,&nbsp;Yi-Ling Liu,&nbsp;Yu-Wen Su,&nbsp;Alan Yueh-Luen Lee,&nbsp;Ya-Wen Chen,&nbsp;Ko-Jiunn Liu,&nbsp;Yunping Luo,&nbsp;Yi-Ren Hong,&nbsp;Tsung-Hsien Chuang","doi":"10.1007/s00262-021-03062-8","DOIUrl":"https://doi.org/10.1007/s00262-021-03062-8","url":null,"abstract":"<p><p>Head and neck cancers are a type of life-threatening cancers characterized by an immunosuppressive tumor microenvironment. Only less than 20% of the patients respond to immune checkpoint blockade therapy, indicating the need for a strategy to increase the efficacy of immunotherapy for this type of cancers. Previously, we identified a type B CpG-oligodeoxynucleotide (CpG-ODN) called CpG-2722, which has the universal activity of eliciting an immune response in grouper, mouse, and human cells. In this study, we further characterized and compared its cytokine-inducing profiles with different types of CpG-ODNs. The antitumor effect of CpG-2722 was further investigated alone and in combination with an immune checkpoint inhibitor in a newly developed syngeneic orthotopic head and neck cancer animal model. Along with other inflammatory cytokines, CpG-2722 induces the gene expressions of interleukin-12 and different types of interferons, which are critical for the antitumor response. Both CpG-2722 and anti-programmed death (PD)-1 alone suppressed tumor growth. Their tumor suppression efficacies were further enhanced when CpG-2722 and anti-PD-1 were used in combination. Mechanistically, CpG-2722 shaped a tumor microenvironment that is favorable for the action of anti-PD-1, which included promoting the expression of different cytokines such as IL-12, IFN-β, and IFN-γ, and increasing the presence of plasmacytoid dendritic cells, M1 macrophages, and CD8 positive T cells. Overall, CpG-2722 provided a priming effect for CD8 positive T cells by sharpening the tumor microenvironment, whereas anti-PD-1 released the brake for their tumor-killing effect, resulting in an enhanced efficacy of the combined CpG-2722 and anti-PD-1.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":"1115-1128"},"PeriodicalIF":5.8,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9016021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39464261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune checkpoint inhibitor-related thrombocytopenia: incidence, risk factors and effect on survival.","authors":"Tyler C Haddad,&nbsp;Songzhu Zhao,&nbsp;Mingjia Li,&nbsp;Sandip H Patel,&nbsp;Andrew Johns,&nbsp;Madison Grogan,&nbsp;Gabriella Lopez,&nbsp;Abdul Miah,&nbsp;Lai Wei,&nbsp;Gabriel Tinoco,&nbsp;Brian Riesenberg,&nbsp;Zihai Li,&nbsp;Alexa Meara,&nbsp;Erin M Bertino,&nbsp;Kari Kendra,&nbsp;Gregory Otterson,&nbsp;Carolyn J Presley,&nbsp;Dwight H Owen","doi":"10.1007/s00262-021-03068-2","DOIUrl":"https://doi.org/10.1007/s00262-021-03068-2","url":null,"abstract":"<p><strong>Introduction: </strong>Immune checkpoint inhibitors (ICI) are associated with unique immune-related adverse events (irAEs). Immune-related thrombocytopenia (irTCP) is an understudied and poorly understood toxicity; little data are available regarding either risk of irTCP or the effect of irTCP on clinical outcomes of patients treated with ICI.</p><p><strong>Methods: </strong>We conducted a retrospective review of sequential cancer patients treated with ICI between 2011 and 2017 at our institution. All patients who received ICI alone or in combination with other systemic therapy in any line of treatment were included; those with thrombocytopenia ≥ grade 3 at baseline were excluded. We calculated the incidence of ≥ grade 3 irTCP and overall survival (OS). Patient factors associated with irTCP were assessed.</p><p><strong>Results: </strong>We identified 1,038 patients that met eligibility criteria. Overall, 89 (8.6%) patients developed grade ≥ 3 thrombocytopenia; eighteen were attributed to ICI (1.73% overall). Patients who developed grade ≥ 3 irTCP had worse overall survival compared to those whose thrombocytopenia was unrelated to ICI (4.17 vs. 10.8 month; HR. 1.94, 95% CI 1.13, 3.33; log-rank p = 0.0164). Patients with grade ≥ 3 irTCP also had worse survival compared to those without thrombocytopenia (4.17 vs. 13.31 months; HR 2.22, 95% CI 1.36, 3.62; log-rank p = 0.001). The incidence of irTCP appeared lowest among those treated with PD-1/L1 monotherapy (p = 0.059) and was not associated with cancer type, smoking status, age, gender, race, or line of therapy.</p><p><strong>Conclusions: </strong>Unlike other irAEs, we found that irTCP was associated with worse overall survival. The incidence of irTCP appeared lowest among those treated with PD-1/L1 monotherapy.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":"1157-1165"},"PeriodicalIF":5.8,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9015999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39493047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of combination treatment with durvalumab plus tremelimumab on the tumor microenvironment in non-small-cell lung carcinoma.","authors":"Li Cheng,&nbsp;Todd Creasy,&nbsp;Fernanda Pilataxi,&nbsp;Lydia Greenlees,&nbsp;Luis Vence,&nbsp;Sriram Sridhar,&nbsp;Katie Streicher","doi":"10.1007/s00262-021-03065-5","DOIUrl":"https://doi.org/10.1007/s00262-021-03065-5","url":null,"abstract":"<p><p>The rapid development of immune checkpoint blockade (ICB) therapies has revolutionized the cancer treatment landscape and brightened the long-term forecast for many cancer patients. However, the specific genomic and proteomic changes in tumors treated with different ICB treatments have yet to be fully characterized. We treated four non-small-cell lung carcinoma (NSCLC) tumor digests ex vivo with the anti-PD-L1 antibody durvalumab (D) alone or in combination with the anti-CTLA-4 antibody tremelimumab (T) to explore changes in gene and protein expression associated with these ICB therapies. All four tumors showed a robust increase in interferon gamma (IFN-γ) production (100-300% higher than isotype control) in both D- and D + T-treated tumors. Three of the four tumors showed additional increases in IFN-γ production with D + T compared with D (40-70%). A substantial reduction in interleukin 10 (IL-10) was also found in three of the four tumors (reduced to 4-8%) in response to D and D + T. Conventional CD4 + /CD8 + populations and T cell activation markers increased after D and D + T treatment. D and D + T upregulated multiple IPA pathways involving T cell activation. D + T resulted in additional upregulation of Th1/Th2 pathways through a different set of genes, as well as greater reduction in genes involved in epithelial-mesenchymal transition (EMT), angiogenesis, and cancer stemness. Our results demonstrated that D + T augmented the effects of D in the microenvironment of this set of NSCLC tumors. The specific impact of D + T on the regulation of EMT, angiogenesis, and cancer stemness warrants further evaluation in a larger set of tumors.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":"1167-1181"},"PeriodicalIF":5.8,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9015996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39497565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic switch of immunity and antitumor effects of metformin in rat spontaneous esophageal carcinogenesis.","authors":"Ryohei Takei,&nbsp;Tomoharu Miyashita,&nbsp;Satoshi Takada,&nbsp;Hidehiro Tajima,&nbsp;Itasu Ninomiya,&nbsp;Hiroyuki Takamura,&nbsp;Sachio Fushida,&nbsp;Ai Harashima,&nbsp;Seiichi Munesue,&nbsp;Shintaro Yagi,&nbsp;Noriyuki Inaki,&nbsp;Tetsuo Ohta,&nbsp;Yasuhiko Yamamoto","doi":"10.1007/s00262-021-03027-x","DOIUrl":"https://doi.org/10.1007/s00262-021-03027-x","url":null,"abstract":"<p><p>Chronic inflammation contributes to tumor development by creating a local microenvironment that facilitates neoplastic transformation and potentiates the progression of cancer. Esophageal cancer (EC) is an inflammation-associated malignancy with a poor prognosis. The nature of the switch between chronic inflammation of the esophagus and EC-related immunological changes remains unclear. Here, we examined the dynamic alterations of immune cells at different stages of chronic esophagitis, Barrett's esophagus (BE) and EC using an esophageal spontaneous carcinogenesis rat model. We also investigated the anticancer effects of metformin. To stimulate EC carcinogenesis, chronic gastroduodenal reflux esophagitis via esophagojejunostomy was induced in 120 rats in metformin-treated and non-treated (control) groups. After 40 weeks, BE and EC developed in 96.7% and 63.3% of the control group, and in 66.7% and 23.3% of the metformin-treated group, respectively. Flow cytometric analysis demonstrated that the balance of M1/M2-polarized or phospho-Stat3-positive macrophages, regulatory T, cytotoxic T, natural killer (NK), NK T cells, and Th17 T cells was dynamically changed at each stage of the disease and were resolved by metformin treatment. These findings clarify the immunity in esophageal carcinogenesis and suggest that metformin could suppress this disease by improving the immunosuppressive tumor microenvironment and immune evasion.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":"777-789"},"PeriodicalIF":5.8,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s00262-021-03027-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39315634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"No evidence that HLA genotype influences the driver mutations that occur in cancer patients.","authors":"Noor Kherreh,&nbsp;Siobhán Cleary,&nbsp;Cathal Seoighe","doi":"10.1007/s00262-021-03028-w","DOIUrl":"https://doi.org/10.1007/s00262-021-03028-w","url":null,"abstract":"<p><p>The major histocompatibility (MHC) molecules are capable of presenting neoantigens resulting from somatic mutations on cell surfaces, potentially directing immune responses against cancer. This led to the hypothesis that cancer driver mutations may occur in gaps in the capacity to present neoantigens that are dependent on MHC genotype. If this is correct, it has important implications for understanding oncogenesis and may help to predict driver mutations based on genotype data. In support of this hypothesis, it has been reported that driver mutations that occur frequently tend to be poorly presented by common MHC alleles and that the capacity of a patient's MHC alleles to present the resulting neoantigens is predictive of the driver mutations that are observed in their tumor. Here we show that these reports of a strong relationship between driver mutation occurrence and patient MHC alleles are a consequence of unjustified statistical assumptions. Our reanalysis of the data provides no evidence of an effect of MHC genotype on the oncogenic mutation landscape.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":"819-827"},"PeriodicalIF":5.8,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s00262-021-03028-w","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39331055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Analysis of T cell receptor clonotypes in tumor microenvironment identifies shared cancer-type-specific signatures.","authors":"Yvonne H F Teng,&nbsp;Hong Sheng Quah,&nbsp;Lisda Suteja,&nbsp;João M L Dias,&nbsp;Annalisa Mupo,&nbsp;Rachael J M Bashford-Rogers,&nbsp;George S Vassiliou,&nbsp;Melvin L K Chua,&nbsp;Daniel S W Tan,&nbsp;Darren W T Lim,&nbsp;N Gopalakrishna Iyer","doi":"10.1007/s00262-021-03086-0","DOIUrl":"https://doi.org/10.1007/s00262-021-03086-0","url":null,"abstract":"","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":"999"},"PeriodicalIF":5.8,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9119220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39540163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Dynamic switch of immunity and antitumor effects of metformin in rat spontaneous esophageal carcinogenesis.","authors":"Ryohei Takei,&nbsp;Tomoharu Miyashita,&nbsp;Satoshi Takada,&nbsp;Hidehiro Tajima,&nbsp;Itasu Ninomiya,&nbsp;Hiroyuki Takamura,&nbsp;Sachio Fushida,&nbsp;Ai Harashima,&nbsp;Seiichi Munesue,&nbsp;Shintaro Yagi,&nbsp;Noriyuki Inaki,&nbsp;Tetsuo Ohta,&nbsp;Yasuhiko Yamamoto","doi":"10.1007/s00262-021-03039-7","DOIUrl":"https://doi.org/10.1007/s00262-021-03039-7","url":null,"abstract":"","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":"791-793"},"PeriodicalIF":5.8,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8921131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39391678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating regulatory T cells predict efficacy and atypical responses in lung cancer patients treated with PD-1/PD-L1 inhibitors.","authors":"Da Hyun Kang,&nbsp;Chaeuk Chung,&nbsp;Pureum Sun,&nbsp;Da Hye Lee,&nbsp;Song-I Lee,&nbsp;Dongil Park,&nbsp;Jeong Suk Koh,&nbsp;Yoonjoo Kim,&nbsp;Hyon-Seung Yi,&nbsp;Jeong Eun Lee","doi":"10.1007/s00262-021-03018-y","DOIUrl":"https://doi.org/10.1007/s00262-021-03018-y","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) have become the standard of care for a variety of cancers, including non-small cell lung cancer (NSCLC). In this study, we investigated the frequency of pseudoprogression and hyperprogression in lung cancer patients treated with ICIs in the real world and aimed to discover a novel candidate marker to distinguish pseudoprogression from hyperprogression soon after ICI treatment.</p><p><strong>Methods: </strong>This study included 74 patients with advanced NSCLC who were treated with PD-1/PD-L1 inhibitors at Chungnam National University Hospital (CNUH) between January 2018 and August 2020. Chest X-rays were examined on day 7 after the first ICI dose to identify changes in the primary mass, and the response was assessed by computed tomography (CT). We evaluated circulating regulatory T (Treg) cells using flow cytometry and correlated the findings with clinical outcomes.</p><p><strong>Results: </strong>The incidence of pseudoprogression was 13.5%, and that of hyperprogression was 8.1%. On day 7 after initiation of treatment, the frequency of CD4⁺CD25⁺CD127^loFoxP3⁺ Treg cells was significantly decreased compared with baseline (P = 0.038) in patients who experienced pseudoprogression and significantly increased compared with baseline (P = 0.024) in patients who experienced hyperprogression. In the responder group, the frequencies of CD4⁺CD25⁺CD127^loFoxP3⁺ Treg cells and PD-1⁺CD4⁺CD25⁺CD127^loFoxP3⁺ Treg cells were significantly decreased 7 days after commencement of treatment compared with baseline (P = 0.034 and P < 0.001, respectively).</p><p><strong>Conclusion: </strong>Circulating Treg cells represent a promising potential dynamic biomarker to predict efficacy and differentiate atypical responses, including pseudoprogression and hyperprogression, after immunotherapy in patients with NSCLC.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":"579-588"},"PeriodicalIF":5.8,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s00262-021-03018-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39197538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiotherapy planning parameters correlate with changes in the peripheral immune status of patients undergoing curative radiotherapy for localized prostate cancer.","authors":"Elgin Hoffmann,&nbsp;Frank Paulsen,&nbsp;Philipp Schaedle,&nbsp;Daniel Zips,&nbsp;Cihan Gani,&nbsp;Hans-Georg Rammensee,&nbsp;Cécile Gouttefangeas,&nbsp;Franziska Eckert","doi":"10.1007/s00262-021-03002-6","DOIUrl":"https://doi.org/10.1007/s00262-021-03002-6","url":null,"abstract":"<p><strong>Purpose: </strong>The influence of radiotherapy on patient immune cell subsets has been established by several groups. Following a previously published analysis of immune changes during and after curative radiotherapy for prostate cancer, this analysis focused on describing correlations of changes of immune cell subsets with radiation treatment parameters.</p><p><strong>Patients and methods: </strong>For 13 patients treated in a prospective trial with radiotherapy to the prostate region (primary analysis) and five patients treated with radiotherapy to prostate and pelvic nodal regions (exploratory analysis), already published immune monitoring data were correlated with clinical data as well as radiation planning parameters such as clinical target volume (CTV) and volumes receiving 20 Gy (V20) for newly contoured volumes of pelvic blood vessels and bone marrow.</p><p><strong>Results: </strong>Most significant changes among immune cell subsets were observed at the end of radiotherapy. In contrast, correlations of age and CD8⁺ subsets (effector and memory cells) were observed early during and 3 months after radiotherapy. Ratios of T cells and T cell proliferation compared to baseline correlated with CTV. Early changes in regulatory T cells (Treg cells) and CD8⁺ effector T cells correlated with V20 of blood vessels and bone volumes.</p><p><strong>Conclusions: </strong>Patient age as well as radiotherapy planning parameters correlated with immune changes during radiotherapy. Larger irradiated volumes seem to correlate with early suppression of anti-cancer immunity. For immune cell analysis during normofractionated radiotherapy and correlations with treatment planning parameters, different time points should be looked at in future projects.</p><p><strong>Trial registration number: </strong>NCT01376674, 20.06.2011.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":"541-552"},"PeriodicalIF":5.8,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s00262-021-03002-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39190898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of S100A9 in the interaction between pancreatic ductal adenocarcinoma cells and stromal cells.","authors":"Pin-Jui Kung,&nbsp;Ting-Yu Lai,&nbsp;Jerry Cao,&nbsp;Li-Chung Hsu,&nbsp;Tsai-Chen Chiang,&nbsp;Pu Ou-Yang,&nbsp;Ching-Yi Tsai,&nbsp;Yi-Fen Tsai,&nbsp;Chih-Wen Lin,&nbsp;Chien-Chia Chen,&nbsp;Meng-Kun Tsai,&nbsp;Yu-Wen Tien,&nbsp;Chih-Yuan Lee","doi":"10.1007/s00262-021-03026-y","DOIUrl":"https://doi.org/10.1007/s00262-021-03026-y","url":null,"abstract":"<p><strong>Background: </strong>A major feature of the microenvironment in pancreatic ductal adenocarcinoma (PDAC) is the significant amount of extracellular matrix produced by pancreatic stellate cells (PSCs), which have been reported to enhance the invasiveness of pancreatic cancer cells and negatively impact the prognosis.</p><p><strong>Methods: </strong>We analyzed the data from two publicly available microarray datasets deposited in the Gene Expression Omnibus and found candidate genes that were differentially expressed in PDAC cells with metastatic potential and PDAC cells cocultured with PSCs. We studied the interaction between PDAC cells and PSCs in vitro and verified our finding with the survival data of patients with PDAC from the website of The Human Protein Atlas.</p><p><strong>Results: </strong>We found that PSCs stimulated PDAC cells to secrete S100A9, which attracted circulatory monocytes into cancer tissue and enhanced the expression of programmed death-ligand 1 (PD-L1) on macrophages. When analyzing the correlation of S100A9 and PD-L1 expression with the clinical outcomes of patients with PDAC, we ascertained that high expression of S100A9 and PD-L1 was associated with poor survival in patients with PDAC.</p><p><strong>Conclusions: </strong>PSCs stimulated PDAC cells to secrete S100A9, which acts as a chemoattractant to attract circulatory monocytes into cancer microenvironment and induces expression of PD-L1 on macrophages. High expression of S100A9 and PD-L1 was associated with worse overall survival in a cohort of patients with PDAC.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":"705-718"},"PeriodicalIF":5.8,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s00262-021-03026-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39306995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}