Oncoimmunology最新文献

{"title":"Arsenic trioxide as an inducer of immunogenic cell death.","authors":"Oliver Kepp, Hui Pan, Peng Liu, Guido Kroemer","doi":"10.1080/2162402X.2023.2174723","DOIUrl":"https://doi.org/10.1080/2162402X.2023.2174723","url":null,"abstract":"Arsenic trioxide (ATO) is often combined with all-trans retinoic acid (ATRA) to treat promyelocytic leukemia (PML) with a rather high success rate. In mice, it has been documented that ATRA is much more efficient against PML developing in immunocompetent than in immunodeficient mice, pleading in favor of the idea that the antileukemic action of ATRA depends on the immune system. However, no such immunedependent effects of ATO have been described in PML. Nonetheless, it has been shown that ATO increases lymphokine activated killer (LAK)-mediated cytotoxicity against human myeloma cells and enhances the efficacy of Bacille Calmette-Guérin (BCG) immunotherapy in a mouse model of bladder cancer. Moreover, ATO has been demonstrated to deplete regulatory T cells in a mouse model of colon cancer. Of note, in a recent paper published in Cellular and Molecular Immunology, Chen et al. demonstrate that ATO can trigger immunogenic cell death (ICD) in solid tumors. The concept of ICD, initially established in cells undergoing apoptosis, has recently been extended to other variants of regulated cell death such as necroptosis, pyroptosis, and ferroptosis. Canonical ICD triggers the emission of a set of danger associated molecular patterns (DAMPs), which act on specific pattern recognition receptors (PRRs) expressed by antigen presenting dendritic cells (DCs), thus stimulating phagocytosis of malignant cells and antigen presentation of tumorassociated antigens by DCs. Mature DCs facilitate crosspresentation of tumor antigens to cytotoxic T lymphocytes (CTL) as well as the education of memory T cells, altogether conferring efficacy to cancer therapies that last beyond treatment discontinuation. Preclinical and clinical data support the notion that ICD inducers can be advantageously combined with additional immunotherapies such as immune checkpoint blockade targeting the PD-1/PD-L1 interaction. In their work, Chen et al. discovered that in vitro cultures of malignant cells with ATO led to the generation of a whole cell vaccine that could be injected into mice to reduce cancer growth in prophylactic as well as in therapeutic settings. These anticancer effects of ATO-treated cancer cells were lost or attenuated upon depletion of CD8 (but not NK1.1) T cells, as well as after blocking either interferon-Υ (IFNΥ) or the Type-1 interferon receptor (IFNAR) with suitable antibodies. ATO-treated cells manifested several well-established hallmarks of ICD including the release of ATP and high-mobility group B1 (HMGB1) protein, the exposure of calreticulin (CALR) on the cell surface, the induction of cGAMP production, and the H151-repressible (and hence likely STINGdependent) induction of interferon-β1 (IFNβ1). At the mechanistic level, the authors described that ATO induced biochemical characteristics of several cellular stress and death routines including autophagy, apoptosis, ferroptosis, necroptosis, and pyroptosis that all were blunted when ATOinduced oxidative stress was","PeriodicalId":19683,"journal":{"name":"Oncoimmunology","volume":"12 1","pages":"2174723"},"PeriodicalIF":7.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9908291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10757420","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":"Mesothelin-targeting T cells bearing a novel T cell receptor fusion construct (TRuC) exhibit potent antitumor efficacy against solid tumors.","authors":"Jian Ding,&nbsp;Sarah Guyette,&nbsp;Brett Schrand,&nbsp;Jessica Geirut,&nbsp;Holly Horton,&nbsp;Guangwu Guo,&nbsp;Greg Delgoffe,&nbsp;Ashley Menk,&nbsp;Patrick A Baeuerle,&nbsp;Robert Hofmeister,&nbsp;Robert Tighe","doi":"10.1080/2162402X.2023.2182058","DOIUrl":"https://doi.org/10.1080/2162402X.2023.2182058","url":null,"abstract":"<p><p>T cell Receptor (TCR) Fusion Construct (TRuC®) T cells harness all signaling subunits of the TCR to activate T cells and eliminate tumor cells, with minimal release of cytokines. While adoptive cell therapy with chimeric antigen receptor (CAR)-T cells has shown unprecedented clinical efficacy against B-cell malignancies, monotherapy with CAR-T cells has suboptimal clinical efficacy against solid tumors, probably because of the artificial signaling properties of the CAR. TRuC-T cells may address the suboptimal efficacy of existing CAR-T therapies for solid tumors. Here, we report that mesothelin (MSLN)-specific TRuC-T cells (referred to as TC-210 T cells) potently kill MSLN+ tumor cells <i>in vitro</i> and efficiently eradicate MSLN+ mesothelioma, lung, and ovarian cancers in xenograft mouse tumor models. When benchmarked against MSLN-targeted BBζ CAR-T cells (MSLN-BBζ CAR-T cells), TC-210 T cells show an overall comparable level of efficacy; however, TC-210 T cells consistently show faster tumor rejection kinetics that are associated with earlier intratumoral accumulation and earlier signs of activation. Furthermore, <i>in vitro</i> and <i>ex vivo</i> metabolic profiling suggests TC-210 T cells have lower glycolytic activity and higher mitochondrial metabolism than MSLN-BBζ CAR-T cells. These data highlight TC-210 T cells as a promising cell therapy for treating MSLN-expressing cancers. The differentiated profile from CAR-T cells may translate into better efficacy and safety of TRuC-T cells for solid tumors.</p>","PeriodicalId":19683,"journal":{"name":"Oncoimmunology","volume":"12 1","pages":"2182058"},"PeriodicalIF":7.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/58/1f/KONI_12_2182058.PMC9980471.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9342160","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":"ELK3-CXCL16 axis determines natural killer cell cytotoxicity via the chemotactic activity of CXCL16 in triple negative breast cancer.","authors":"Hae-Yun Jung,&nbsp;Dae-Keum Lee,&nbsp;Minwook Lee,&nbsp;Seung Hee Choi,&nbsp;Joo Dong Park,&nbsp;Eun-Su Ko,&nbsp;Jongwon Lee,&nbsp;Kyung-Soon Park,&nbsp;Hae-Yun Jung","doi":"10.1080/2162402X.2023.2190671","DOIUrl":"https://doi.org/10.1080/2162402X.2023.2190671","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is the most challenging subtype of breast cancer because of its aggressive behavior and the limited therapeutic strategies available. In the last decade, immunotherapy has become a promising treatment to prolong survival in advanced solid cancers including TNBC. However, the efficacy of immunotherapy in solid cancers remains limited because solid tumors contain few tumor-infiltrating lymphocytes. Here, we show that targeting an ETS transcription factor ELK3 (ELK3) recruits immune cells including natural killer (NK) cells into tumors via the chemotactic activity of chemokine. ELK3 depletion increases CXCL16 expression level and promotes NK cell cytotoxicity through CXCL16-mediated NK cell recruitment in TNBC. <i>In silico</i> analysis showed that <i>ELK3</i> is negatively correlated with <i>CXCL16</i> expression in breast cancer patient samples. Low expression of <i>ELK3</i> and high expression of <i>CXCL16</i> were associated with a better prognosis. Low expression of <i>ELK3</i> and high expression of <i>CXCL16</i> were associated with increased expression of NK cell-related genes. Our findings demonstrate that the ELK3-CXCL16 axis modulates NK cell recruitment to increase NK cell cytotoxicity, suggesting that targeting the <i>ELK3</i> gene could be an adjuvant strategy for increasing the efficacy of immunotherapy in TNBC.</p>","PeriodicalId":19683,"journal":{"name":"Oncoimmunology","volume":"12 1","pages":"2190671"},"PeriodicalIF":7.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3c/77/KONI_12_2190671.PMC10026901.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9399689","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":"T-cell dysfunction in natural killer/T-cell lymphoma.","authors":"Xiaoyan Feng,&nbsp;Miaomiao Meng,&nbsp;Hongwen Li,&nbsp;Yuyang Gao,&nbsp;Wenting Song,&nbsp;Ruiqing Di,&nbsp;Zhaoming Li,&nbsp;Xudong Zhang,&nbsp;Mingzhi Zhang","doi":"10.1080/2162402X.2023.2212532","DOIUrl":"https://doi.org/10.1080/2162402X.2023.2212532","url":null,"abstract":"<p><p>Natural killer/T-cell lymphoma (NKTCL) is an incurable aggressive T-cell lymphoma closely correlated with Epstein‒Barr virus (EBV) infection. Chronic and consistent viral infection induces T-cell exhaustion. Herein, we describe T-cell dysfunction in NKTCL patients for the first time. Peripheral blood mononuclear cells (PBMCs) from age-matched healthy donors (HDs) and NKTCL patients were collected, and lymphocyte distributions, multiple surface inhibitory receptors (IRs), effector cytokine production and cell proliferation were determined by flow cytometry. PBMCs from HDs were cocultured with NKTCL cell lines to verify the clinical findings. IR expression was further assessed in NKTCL tumor biopsies using multiplex immunohistochemistry (mIHC). NKTCL patients have higher frequencies than HDs of inhibitory T regulatory cells (Tregs) and myeloid-derived suppressor cells (MDSCs). T-cell distribution also varies between NKTCL patients and HDs. T cells from NKTCL patients demonstrated higher expression levels of multiple IRs than HDs. Meanwhile, T-cell proliferation and interferon-γ production was significantly reduced in NKTCL patients. More importantly, the number of EBV-specific cytotoxic cells was lower in NTKCL patients, and these cells demonstrated upregulation of multiple IRs and secreted fewer effector cytokines. Interestingly, NKTCL cells caused normal PBMCs to acquire T-cell exhaustion phenotypes and induced generation of Tregs and MDSCs. In line with ex vivo finding, mIHC results showed that CD8+ T cells from NKTCL tumor biopsies expressed much higher level of IRs compared with reactive lymphoid hyperplasia individuals. The immune microenvironment of NKTCL patients exhibited T-cell dysfunction and accumulation of inhibitory cell components, which may contribute to impaired antitumor immunity.</p>","PeriodicalId":19683,"journal":{"name":"Oncoimmunology","volume":"12 1","pages":"2212532"},"PeriodicalIF":7.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f2/c0/KONI_12_2212532.PMC10210841.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10545097","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":"Daratumumab induces cell-mediated cytotoxicity of primary effusion lymphoma and is active against refractory disease.","authors":"Prabha Shrestha,&nbsp;Yana Astter,&nbsp;David A Davis,&nbsp;Ting Zhou,&nbsp;Constance M Yuan,&nbsp;Ramya Ramaswami,&nbsp;Hao-Wei Wang,&nbsp;Kathryn Lurain,&nbsp;Robert Yarchoan","doi":"10.1080/2162402X.2022.2163784","DOIUrl":"https://doi.org/10.1080/2162402X.2022.2163784","url":null,"abstract":"<p><p>Primary effusion lymphoma (PEL), an aggressive non-Hodgkin lymphoma caused by Kaposi sarcoma-associated herpesvirus (KSHV), lacks standard therapy and has a median survival of 10-22 months with combination chemotherapy. PEL is a tumor of plasmablast-like B cells generally expressing CD38, the target of daratumumab (Dara). Initially, we assessed PEL cells from eight patients and established that each expressed high levels of CD38 by flow cytometry. PEL cell lines were also evaluated and most had high CD38 expression. We then assessed Dara's effects on complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) of PEL cell lines as well as its clinical benefits on two patients with PEL. Despite high CD38 expression, Dara did not induce CDC of PEL cell lines, due in part to high levels of the complement-inhibitory proteins, CD55 and CD59. However, Dara induced significant and dose-dependent increases in ADCC, particularly in those lines with high CD38 levels. Two FDA-approved drugs, all trans-retinoic acid (ATRA) and pomalidomide (Pom), significantly increased surface CD38 levels in low-CD38 expressing PEL cell lines, resulting in increased Dara-induced ADCC. Two patients with refractory PEL were treated with Dara alone or in combination with Pom. One patient with leptomeningeal PEL had a complete response to Dara and Pom combination treatment. Others had improvement in performance status and resolution of malignant ascites with Dara alone. Together, these data support the use of Dara monotherapy or in combination with ATRA or Pom as a potential therapeutic option for PEL.</p>","PeriodicalId":19683,"journal":{"name":"Oncoimmunology","volume":"12 1","pages":"2163784"},"PeriodicalIF":7.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9828731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10761982","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: Toll-like receptor ligands in cancer therapy.","authors":"Julie Le Naour,&nbsp;Guido Kroemer","doi":"10.1080/2162402X.2023.2180237","DOIUrl":"https://doi.org/10.1080/2162402X.2023.2180237","url":null,"abstract":"<p><p>Accumulating evidence indicates that Toll-like receptor (TLR) agonists proficiently (re)instore cancer immunosurveillance as immunological adjuvants. So far, three TLR agonists have been approved by regulatory agencies for use in oncological applications. Additionally, these immunotherapeutics have been extensively investigated over the past few years. Multiple clinical trials are currently evaluating the combination of TLR agonists with chemotherapy, radiotherapy, or different immunotherapies. Moreover, antibodies targeting tumor-enriched surface proteins that have been conjugated to TLR agonists are being developed to stimulate anticancer immune responses specifically within the tumor microenvironment. Solid preclinical and translational results support the favorable immune-activating effects of TLR agonists. Here, we summarize recent preclinical and clinical advances in the development of TLR agonists for anticancer immunotherapy.</p>","PeriodicalId":19683,"journal":{"name":"Oncoimmunology","volume":"12 1","pages":"2180237"},"PeriodicalIF":7.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ad/65/KONI_12_2180237.PMC9980677.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9342159","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":"Acquired DNA damage repairs deficiency-driven immune evolution and involved immune factors of local versus distant metastases in non-small cell lung cancer.","authors":"Wen-Fang Tang,&nbsp;Xiao-Jun Fan,&nbsp;Hua Bao,&nbsp;Rui Fu,&nbsp;Yi Liang,&nbsp;Min Wu,&nbsp;Chao Zhang,&nbsp;Jian Su,&nbsp;Yi-Long Wu,&nbsp;Wen-Zhao Zhong","doi":"10.1080/2162402X.2023.2215112","DOIUrl":"https://doi.org/10.1080/2162402X.2023.2215112","url":null,"abstract":"<p><p>The evolution of immune profile from primary tumors to distant and local metastases in non-small cell lung cancer (NSCLC), as well as the impact of the immune background of primary tumors on metastatic potential, remains unclear. To address this, we performed whole-exome sequencing and immunohistochemistry for 73 paired primary and metastatic tumor samples from 41 NSCLC patients, and analyzed the change of immune profile from primary tumors to metastases and involved genetic factors. We found that distant metastases tended to have a decreased CD8+ T cell level along with an increased chromosomal instability (CIN) compared with primary tumors, which was partially ascribed to acquired DNA damage repair (DDR) deficiency. Distant metastases were characterized by immunosuppression (low CD8+ T cell level) and immune evasion (high PD-L1 level) whereas local metastases (pleura) were immune-competent with high CD8+ T cell, low CD4+ T cell and low PD-L1 level. Primary tumors with high levels of CD4+ T cells were associated with distant metastases rather than local metastases. Analysis of TCGA data and a single-cell RNA-sequencing dataset revealed a decreasing trend of major immune cells, such as CD8+ T cells, and an increasing trend of CD4 T helper cells (Th2 and Th1) in primary tumors with metastases from local to distant sites. Our study indicates that there are differences in the immune evolution between distant and local metastases, and that acquired DDR deficiency contributes to the immunosuppression in distant metastases of NSCLC. Moreover, the immune background of primary tumors may affect their metastatic potential.</p>","PeriodicalId":19683,"journal":{"name":"Oncoimmunology","volume":"12 1","pages":"2215112"},"PeriodicalIF":7.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/be/c2/KONI_12_2215112.PMC10228401.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10195654","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":"CD8 T cell-mediated depletion of HBV surface-antigen-expressing, bilineal-differentiated liver carcinoma cells generates highly aggressive escape variants.","authors":"Na Qiu,&nbsp;Akshaya Srikanth,&nbsp;Medhanie Mulaw,&nbsp;Umesh Tharehalli,&nbsp;Shanthiya Selvachandran,&nbsp;Martin Wagner,&nbsp;Thomas Seufferlein,&nbsp;Katja Stifter,&nbsp;André Lechel,&nbsp;Reinhold Schirmbeck","doi":"10.1080/2162402X.2023.2215096","DOIUrl":"https://doi.org/10.1080/2162402X.2023.2215096","url":null,"abstract":"<p><p>The expression of viral antigens in chronic hepatitis B virus (HBV) infection drives continuous liver inflammation, one of the main risk factors to develop liver cancer. HBV developed immune-suppressive functions to escape from the host immune system, but their link to liver tumor development is not well understood. Here, we analyzed if and how HBV surface antigen (HBs) expression in combined hepatocellular-cholangiocarcinoma (cHCC/iCCA) cells influences their antigenicity for CD8 T cells. We randomly isolated liver tumor tissues from AlfpCre⁺-Trp53^fl/fl/Alb-HBs⁺ tg mice and established primary carcinoma cell lines (pCCL) that showed a bilineal (CK7⁺/HNF4α⁺) cHCC/iCCA phenotype. These pCCL uniformly expressed HBs (HBs^hi), and low levels of MHC-I (MHC-I^lo), and were transiently convertible to a high antigenicity (MHC-I^hi) phenotype by IFN-γ treatment. HBs^hi/pCCL induced HBs/(K^b/S_190-197)-specific CD8 T cells and developed slow-growing tumors in subcutaneously transplanted C57Bl/6J (B6) mice. Interestingly, pCCL-ex cells, established from HBs^hi/pCCL-induced and re-explanted tumors in B6 but not those in immune-deficient Rag1^-/- mice showed major alterations, like an MHC-I^hi phenotype, a prominent growth-biased gene expression signature, a significantly decreased HBs expression (HBs^lo) and a switch to fast-growing tumors in re-transplanted B6 or PD-1^-/- hosts with an unlocked PD-1/PD-L1 control system. CD8 T cell-mediated elimination of HBs^hi/pCCL, together with the attenuation of the negative restraints of HBs in the tumor cells, like ER-stress, reveals a novel mechanism to unleash highly aggressive HBs^lo/pCCL-ex immune-escape variants. Under certain conditions, HBs-specific CD8 T-cell responses thus potentiate tumor growth, an aspect that should be considered for therapeutic vaccination strategies against chronic HBV infection and liver tumors.</p>","PeriodicalId":19683,"journal":{"name":"Oncoimmunology","volume":"12 1","pages":"2215096"},"PeriodicalIF":7.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/60/a3/KONI_12_2215096.PMC10228399.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10195656","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":"Microbiota-associated immunotherapy resistance caused by deficient PD-L2 - RGMb signaling.","authors":"Marine Fidelle,&nbsp;Isabelle Lebhar,&nbsp;Laurence Zitvogel,&nbsp;Guido Kroemer","doi":"10.1080/2162402X.2023.2224679","DOIUrl":"https://doi.org/10.1080/2162402X.2023.2224679","url":null,"abstract":"<p><p>In a recent paper in <i>Nature</i>, Park <i>et al</i>. propose a mechanism through which intestinal dysbiosis compromises the efficacy of immunotherapy targeting the PD-L1/PD-1 interaction. Dysbiosis may upregulate a pair of checkpoint molecules, i.e. PD-L2 interacting with RGMb. Antibodies targeting PD-L2/RGMb can restore responses to PD-1 blockade in the context of dysbiosis.</p>","PeriodicalId":19683,"journal":{"name":"Oncoimmunology","volume":"12 1","pages":"2224679"},"PeriodicalIF":7.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/09/12/KONI_12_2224679.PMC10308862.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10196640","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":"Expression of <i>OLR1</i> gene on tumor-associated macrophages of head and neck squamous cell carcinoma, and its correlation with clinical outcome.","authors":"Peng Zhang,&nbsp;Yan Zhao,&nbsp;Xin Xia,&nbsp;Song Mei,&nbsp;Yixuan Huang,&nbsp;Yingying Zhu,&nbsp;Shuting Yu,&nbsp;Xingming Chen","doi":"10.1080/2162402X.2023.2203073","DOIUrl":"https://doi.org/10.1080/2162402X.2023.2203073","url":null,"abstract":"<p><p>Head and neck squamous cell carcinoma (HNSCC) is one of the most heavily immune infiltrated human tumors, having distinct immune subtypes associated with different molecular characteristics and clinical outcomes. The tumor microenvironment (TME) of HNSCC which was dominated by tumor-associated macrophages (TAMs) had a relatively inferior prognosis. High levels of oxidized low-density lipoprotein receptor 1 (<i>OLR1</i>) expression are associated with more aggressive and metastatic characteristics in multiple cancers. However, the link between the <i>OLR1</i> expression and immunosuppression of TME, and the molecular mechanisms which govern intratumoral TAMs behavior are unclear. Here, we performed the transcriptional analysis based on a single-cell RNA-sequencing (scRNA-seq) dataset of HNSCC, and found that the <i>OLR1</i> expression was specifically enriched on the TAMs. Evaluation of protein expression within histologic sections of primary HNSCC patient samples showed a co-expression pattern of <i>OLR1</i> and <i>CD68</i> on macrophages. A total of 498 tumor samples of HNSCC patients from The Cancer Genome Atlas (TCGA) database were also analyzed. Remarkably, <i>OLR1</i> expression was dramatically higher in HNSCC tissues than that in adjacent normal tissues, and the patients with high levels of <i>OLR1</i> expression had significantly unfavorable overall survival (Hazard Ratio = 1.724, log-rank <i>P</i>-value = 0.0066) when compared to patients harboring low expression levels of <i>OLR1</i>. In summary, we reported that the specific expression of <i>OLR1</i> on the TAMs was significantly correlated with poor survival outcomes, revealing that <i>OLR1</i> could serve as a potential prognosis marker and promising target for immunotherapy in HNSCC.</p>","PeriodicalId":19683,"journal":{"name":"Oncoimmunology","volume":"12 1","pages":"2203073"},"PeriodicalIF":7.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0a/c2/KONI_12_2203073.PMC10120517.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9398014","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}