Oncoimmunology最新文献

{"title":"A Chemically Defined TLR3 Agonist with Anticancer Activity.","authors":"Julie Le Naour,&nbsp;Sylvain Thierry,&nbsp;Sarah Adriana Scuderi,&nbsp;Mathilde Boucard-Jourdin,&nbsp;Peng Liu,&nbsp;Marc Bonnin,&nbsp;Yuhong Pan,&nbsp;Clémence Perret,&nbsp;Liwei Zhao,&nbsp;Misha Mao,&nbsp;Chloé Renoux,&nbsp;María Pérez-Lanzón,&nbsp;Baptiste Martin,&nbsp;Oliver Kepp,&nbsp;Guido Kroemer,&nbsp;Bettina Werlé","doi":"10.1080/2162402X.2023.2227510","DOIUrl":"https://doi.org/10.1080/2162402X.2023.2227510","url":null,"abstract":"<p><p>Toll-like receptor 3 (TLR3) agonists such as polyinosinic:polycytidylic acid (poly(I:C)) have immunostimulatory effects that can be taken advantage of to induce anticancer immune responses in preclinical models. In addition, poly(I:C) has been introduced into clinical trials to demonstrate its efficacy as an adjuvant and to enhance the immunogenicity of locally injected tumors, thus reverting resistance to PD-L1 blockade in melanoma patients. Here, we report the pharmacokinetic, pharmacodynamic, mechanistic and toxicological profile of a novel TLR3 agonist, TL-532, a chemically synthesized double-stranded RNA that is composed by blocks of poly(I:C) and poly(A:U) (polyadenylic - polyuridylic acid). In preclinical models, we show that TL-532 is bioavailable after parenteral injection, has an acceptable toxicological profile, and stimulates the production of multiple chemokines and interleukins that constitute pharmacodynamic markers of its immunostimulatory action. When given at a high dose, TL-532 monotherapy reduced the growth of bladder cancers growing on mice. In addition, in immunodeficient mice lacking formylpeptide receptor-1 (FPR1), TL-532 was able to restore the response of orthotopic subcutaneous fibrosarcoma to immunogenic chemotherapy. Altogether, these findings may encourage further development of TL-532 as an immunotherapeutic anticancer agent.</p>","PeriodicalId":19683,"journal":{"name":"Oncoimmunology","volume":"12 1","pages":"2227510"},"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/4c/ec/KONI_12_2227510.PMC10305499.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10196188","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":"Tertiary lymphoid structures in desmoplastic melanoma have increased lymphocyte density, lymphocyte proliferation, and immune cross talk with tumor when compared to non-desmoplastic melanomas.","authors":"Nicole L Edmonds,&nbsp;Sarah E Gradecki,&nbsp;Priya Katyal,&nbsp;Kevin T Lynch,&nbsp;Anne M Stowman,&nbsp;Alejandro A Gru,&nbsp;Victor H Engelhard,&nbsp;Craig L Slingluff,&nbsp;Ileana S Mauldin","doi":"10.1080/2162402X.2022.2164476","DOIUrl":"https://doi.org/10.1080/2162402X.2022.2164476","url":null,"abstract":"<p><p>Tertiary lymphoid structures (TLS) are ectopic lymphoid structures that can arise in human cancers and are associated with improved overall survival (OS) and response to immune checkpoint blockade (ICB) in several cancers, including non-desmoplastic metastatic melanoma (NDMM). Desmoplastic melanoma (DM) has one of the highest response rates to ICB, and we previously identified that primary DM (PDM) contains TLS. Despite the association of TLS with survival and ICB response, it is unknown whether TLS or associated markers of immune activity can differ between PDM and NDMM. We hypothesized that PDM would contain higher frequencies of TLS than NDMM, that T and B-cell densities and proliferation would be greater in TLS of PDM than TLS of NDMM, and that proliferation rates of T and B-cells in PDM TLS would be concordant with those of intratumoral lymphocytes. We found that four features of TLS in PDM distinguish them from TLS in NDMM. TLS were peritumoral in NDMM but intratumoral in PDM. CD8⁺ T-cell and CD20⁺ B-cell densities and proliferative fractions were higher in PDM TLS than NDMM TLS. Additionally, the proliferative fractions of T- and B-cells were concordant between the TLS and tumor site in PDM and discordant in NDMM. Collectively, these data suggest that TLS and associated immune markers can differ across melanoma subsets and suggest that PDM TLS may be more immunologically active and have enhanced immune cell trafficking between tumor and TLS compared to NDMM.</p>","PeriodicalId":19683,"journal":{"name":"Oncoimmunology","volume":"12 1","pages":"2164476"},"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/65/KONI_12_2164476.PMC9828737.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10753113","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":"Tumor-infiltrating lymphocytes for melanoma immunotherapy.","authors":"Oliver Kepp,&nbsp;Peng Liu,&nbsp;Laurence Zitvogel,&nbsp;Guido Kroemer","doi":"10.1080/2162402X.2023.2175506","DOIUrl":"https://doi.org/10.1080/2162402X.2023.2175506","url":null,"abstract":"Oncological routine has incorporated the regular use of monoclonal antibodies targeting checkpoints of T cell function such as ipilimumab, which blocks cytotoxic T-lymphocyte–associated protein 4 (CTLA-4), or pembrolizumab and nivolumab, which both inhibit programmed cell death 1 (PD-1). Such immune checkpoint inhibitors have substantially improved recurrence-free survival (RFS) in patients with advanced stage melanoma. Moreover, the development of molecularly targeted therapies such as the BRAF inhibitor dabrafenib and the mitogen-activated protein inhibitor trametinib has extended treatment options for melanoma patients with advanced metastatic disease. Based on its survival benefits, ipilimumab was the first immune checkpoint blocker approved for the treatment of advanced melanoma. However, high-grade immune-related adverse effects are observed in 23% of patients. Moreover, in a large clinical trial enrolling 834 advanced melanoma patients, pembrolizumab was shown to cause prolonged progressionfree and overall survival with less high-grade toxicity than ipilimumab. For this reason, currently, ipilimumab is used as second-line treatment in patients with metastatic melanoma, whereas PD-1 inhibitors alone or in combination with ipilimumab have been moved to first-line, inducing responses in 45% or 58% of patients, respectively. Nonetheless, double immune checkpoint blockade targeting PD-1 plus CTLA-4 is associated with a high incidence of severe adverse effects and is currently recommended primarily for patients with poor prognostic factors. An activating mutation in the B-Raf proto-oncogene serine/ threonine kinase (BRAF) gene (BRAF) is present in more than 50% of melanoma patients. Thus, combination of dabrafenib plus trametinib is yet another treatment option for melanoma harboring such mutation. Although this therapy is associated with a high initial response rate, most patients develop resistance over time. Further combination approaches involving BRAF inhibition plus immune checkpoint blockade as well as the use of novel immune checkpoint blocking antibodies targeting lymphocyte-activation gene 3 (LAG-3) LAG3 have shown promising response rates. Thus, combination of anti-PD-1 and anti-LAG3 monoclonal antibodies has been associated with objective responses in 16% of patients with refractory disease but follow-up data are still missing. Nevertheless, as it stands the efficacy of both immune checkpoint inhibition or targeted approaches for patients with advanced stage melanoma remains limited and despite optimal treatment about half of the patients will eventually die from the disease. Pioneered by Steven Rosenberg and colleagues, adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) has been developed. This approach necessitates the ex vivo outgrowth and expansion of TILs, followed by their intravenous reinfusion into patients that have undergone preparative lymphodepletion by chemotherapy. The administration of recombinant human i","PeriodicalId":19683,"journal":{"name":"Oncoimmunology","volume":"12 1","pages":"2175506"},"PeriodicalIF":7.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9908292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10757419","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":"Altered phenotypic and metabolic characteristics of FOXP3⁺CD3⁺CD56⁺ natural killer T (NKT)-like cells in human malignant pleural effusion.","authors":"Zi-Hao Wang,&nbsp;Pei Zhang,&nbsp;Wen-Bei Peng,&nbsp;Lin-Lin Ye,&nbsp;Xuan Xiang,&nbsp;Xiao-Shan Wei,&nbsp;Yi-Ran Niu,&nbsp;Si-Yu Zhang,&nbsp;Qian-Qian Xue,&nbsp;Hao-Lei Wang,&nbsp;Qiong Zhou","doi":"10.1080/2162402X.2022.2160558","DOIUrl":"https://doi.org/10.1080/2162402X.2022.2160558","url":null,"abstract":"<p><p>Malignant pleural effusion (MPE) is a functional 'cold' tumor microenvironment in which the antitumor activity of CD8⁺ T cells and natural killer T (NKT)-like cells is suppressed and the function of regulatory T (T_reg) cells is enhanced. Using flow cytometry and immunofluorescence staining, we detected a distinct subset of NKT-like cells expressing FOXP3 in MPE. Through single-cell RNA sequencing (scRNA-seq) analysis, we found that the glycolysis pathway and pyruvate metabolism were highly activated in FOXP3⁺ NKT-like cells. Similar to T_reg cells, FOXP3⁺ NKT-like cells highly expressed monocarboxylate transporter 1 (MCT1) and lactate dehydrogenase B to uptake and utilize lactate, thereby maintaining their immunosuppressive function and hyperlactylation in MPE. Furthermore, we found that MCT1 small molecule inhibitor 7ACC2 significantly reduced FOXP3 expression and histone lactylation levels in NKT-like cells in vitro. In conclusion, we reveal for the first time the altered phenotypic and metabolic features of FOXP3⁺ NKT-like cells in human MPE.</p>","PeriodicalId":19683,"journal":{"name":"Oncoimmunology","volume":"12 1","pages":"2160558"},"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/1f/11/KONI_12_2160558.PMC9788685.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10852338","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":"Melanoma-associated repair-like Schwann cells suppress anti-tumor T-cells via 12/15-LOX/COX2-associated eicosanoid production.","authors":"Oleg Kruglov,&nbsp;Kavita Vats,&nbsp;Vishal Soman,&nbsp;Vladimir A Tyurin,&nbsp;Yulia Y Tyurina,&nbsp;Jiefei Wang,&nbsp;Li'an Williams,&nbsp;Jiying Zhang,&nbsp;Cara Donahue Carey,&nbsp;Erik Jaklitsch,&nbsp;Uma R Chandran,&nbsp;Hülya Bayir,&nbsp;Valerian E Kagan,&nbsp;Yuri L Bunimovich","doi":"10.1080/2162402X.2023.2192098","DOIUrl":"https://doi.org/10.1080/2162402X.2023.2192098","url":null,"abstract":"<p><p>Peripheral glia, specifically the Schwann cells (SCs), have been implicated in the formation of the tumor microenvironment (TME) and in cancer progression. However, <i>in vivo</i> and <i>ex vivo</i> analyses of how cancers reprogram SC functions in different organs of tumor-bearing mice are lacking. We generated Plp1-CreERT/tdTomato mice which harbor fluorescently labeled myelinated and non-myelin forming SCs. We show that this model enables the isolation of the SCs with high purity from the skin and multiple other organs. We used this model to study phenotypic and functional reprogramming of the SCs in the skin adjacent to melanoma tumors. Transcriptomic analyses of the peritumoral skin SCs versus skin SCs from tumor-free mice revealed that the former existed in a repair-like state typically activated during nerve and tissue injury. Peritumoral skin SCs also downregulated pro-inflammatory genes and pathways related to protective anti-tumor responses. <i>In vivo</i> and <i>ex vivo</i> functional assays confirmed immunosuppressive activities of the peritumoral skin SCs. Specifically, melanoma-reprogrammed SCs upregulated 12/15-lipoxygenase (12/15-LOX) and cyclooxygenase (COX)-2, and increased production of anti-inflammatory polyunsaturated fatty acid (PUFA) metabolites prostaglandin E2 (PGE2) and lipoxins A4/B4. Inhibition of 12/15-LOX or COX2 in SCs, or EP4 receptor on lymphocytes reversed SC-dependent suppression of anti-tumor T-cell activation. Therefore, SCs within the skin adjacent to melanoma tumors demonstrate functional switching to repair-like immunosuppressive cells with dysregulated lipid oxidation. Our study suggests the involvement of the melanoma-associated repair-like peritumoral SCs in the modulation of locoregional and systemic anti-tumor immune responses.</p>","PeriodicalId":19683,"journal":{"name":"Oncoimmunology","volume":"12 1","pages":"2192098"},"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/2f/5c/KONI_12_2192098.PMC10044150.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10054584","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 mechanism of IL-34-induced resistance against cytotoxic anti-cancer therapies such as radiation by X-ray and chemotherapy by Oxaliplatin.","authors":"Nanumi Han,&nbsp;Haruka Wada,&nbsp;Takuto Kobayashi,&nbsp;Ryo Otsuka,&nbsp;Ken-Ichiro Seino","doi":"10.1080/2162402X.2023.2238499","DOIUrl":"https://doi.org/10.1080/2162402X.2023.2238499","url":null,"abstract":"<p><p>Interleukin-34 (IL-34) has been known as a factor that is involved with tumor progression and therapeutic resistance. However, there are limitations to addressing the mechanism of how IL-34 induces therapeutic resistance. Here, we show a mechanism of IL-34-induced resistance against cytotoxic anti-cancer therapies such as radiotherapy using X-ray and chemotherapy by Oxaliplatin. This research demonstrates that IL-34 immunologically changes the tumor microenvironment after treatments with radiation or chemotherapeutic agents such as oxaliplatin. We identified the changes in immune cells using flow cytometry and immunofluorescent (IF) staining, which are up-regulated upon the existence of IL-34. Overall, these findings demonstrate the possibility of IL-34 blockade as a novel combination therapy for cancer.</p>","PeriodicalId":19683,"journal":{"name":"Oncoimmunology","volume":"12 1","pages":"2238499"},"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/ef/12/KONI_12_2238499.PMC10392724.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10197711","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: chemotherapy-induced immunogenic cell death in oncology.","authors":"Jenny Sprooten,&nbsp;Raquel S Laureano,&nbsp;Isaure Vanmeerbeek,&nbsp;Jannes Govaerts,&nbsp;Stefan Naulaerts,&nbsp;Daniel M Borras,&nbsp;Lisa Kinget,&nbsp;Jitka Fucíková,&nbsp;Radek Špíšek,&nbsp;Lenka Palová Jelínková,&nbsp;Oliver Kepp,&nbsp;Guido Kroemer,&nbsp;Dmitri V Krysko,&nbsp;An Coosemans,&nbsp;Rianne D W Vaes,&nbsp;Dirk De Ruysscher,&nbsp;Steven De Vleeschouwer,&nbsp;Els Wauters,&nbsp;Evelien Smits,&nbsp;Sabine Tejpar,&nbsp;Benoit Beuselinck,&nbsp;Sigrid Hatse,&nbsp;Hans Wildiers,&nbsp;Paul M Clement,&nbsp;Peter Vandenabeele,&nbsp;Laurence Zitvogel,&nbsp;Abhishek D Garg","doi":"10.1080/2162402X.2023.2219591","DOIUrl":"https://doi.org/10.1080/2162402X.2023.2219591","url":null,"abstract":"<p><p>Immunogenic cell death (ICD) refers to an immunologically distinct process of regulated cell death that activates, rather than suppresses, innate and adaptive immune responses. Such responses culminate into T cell-driven immunity against antigens derived from dying cancer cells. The potency of ICD is dependent on the immunogenicity of dying cells as defined by the antigenicity of these cells and their ability to expose immunostimulatory molecules like damage-associated molecular patterns (DAMPs) and cytokines like type I interferons (IFNs). Moreover, it is crucial that the host's immune system can adequately detect the antigenicity and adjuvanticity of these dying cells. Over the years, several well-known chemotherapies have been validated as potent ICD inducers, including (but not limited to) anthracyclines, paclitaxels, and oxaliplatin. Such ICD-inducing chemotherapeutic drugs can serve as important combinatorial partners for anti-cancer immunotherapies against highly immuno-resistant tumors. In this Trial Watch, we describe current trends in the preclinical and clinical integration of ICD-inducing chemotherapy in the existing immuno-oncological paradigms.</p>","PeriodicalId":19683,"journal":{"name":"Oncoimmunology","volume":"12 1","pages":"2219591"},"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/a3/9a/KONI_12_2219591.PMC10240992.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10184302","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":"Bile acids regulate MAdCAM-1 expression to link the gut microbiota to cancer immunosurveillance.","authors":"Marine Fidelle,&nbsp;Ai-Ling Tian,&nbsp;Laurence Zitvogel,&nbsp;Guido Kroemer","doi":"10.1080/2162402X.2023.2224672","DOIUrl":"https://doi.org/10.1080/2162402X.2023.2224672","url":null,"abstract":"<p><p>In a recent paper in <i>Science</i>, Fidelle et al. unravel a gut immune checkpoint that is subverted by antibiotic treatment. Post-antibiotic dysbiosis of the ileum causes an increase in bile acids that downregulate MAdCAM-1, thereby triggering the exodus of immunosuppressive T cells from gut-associated lymphoid tissues toward tumors.</p>","PeriodicalId":19683,"journal":{"name":"Oncoimmunology","volume":"12 1","pages":"2224672"},"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/cf/62/KONI_12_2224672.PMC10316723.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10195135","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":"Light on life: immunoscore immune-checkpoint, a predictor of immunotherapy response.","authors":"Assia Hijazi,&nbsp;Carlotta Antoniotti,&nbsp;Chiara Cremolini,&nbsp;Jérôme Galon","doi":"10.1080/2162402X.2023.2243169","DOIUrl":"https://doi.org/10.1080/2162402X.2023.2243169","url":null,"abstract":"<p><p>In the last decade, a plethora of immunotherapeutic strategies have been designed to modulate the tumor immune microenvironment. In particular, immune checkpoint (IC) blockade therapies present the most promising advances made in cancer treatment in recent years. In non-small cell lung cancer (NSCLC), biomarkers predicting response to IC treatments are currently lacking. We have recently identified Immunoscore-IC, a powerful biomarker that predicts the efficiency of immune-checkpoint inhibitors (ICIs) in NSCLC patients. Immunoscore-IC is an in vitro diagnostic assay that quantifies densities of PD-L1+, CD8+ cells, and distances between CD8+ and PD-L1+ cells in the tumor microenvironment. Immunoscore-IC can classify responder <i>vs</i> non-responder NSCLC patients for ICIs therapy and is revealed as a promising predictive marker of response to anti-PD-1/PD-L1 immunotherapy in these patients. Immunoscore-IC has also shown a significant predictive value, superior to the currently used PD-L1 marker. In colorectal cancer (CRC), the addition of atezolizumab to first-line FOLFOXIRI plus bevacizumab improved progression-free survival (PFS) in patients with previously untreated metastatic CRC. In the AtezoTRIBE trial, Immunoscore-IC emerged as the first biomarker with robust predictive value in stratifying pMMR metastatic CRC patients who critically benefit from checkpoint inhibitors. Thus, Immunoscore-IC could be a universal biomarker to predict response to PD-1/PD-L1 checkpoint inhibitor immunotherapy across multiple cancer indications. Therefore, cancer patient stratification (by Immunoscore-IC), based on the presence of T lymphocytes and PD-L1 potentially provides support for clinicians to guide them through combination cancer treatment decisions.</p>","PeriodicalId":19683,"journal":{"name":"Oncoimmunology","volume":"12 1","pages":"2243169"},"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/4d/0f/KONI_12_2243169.PMC10405746.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10196220","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":"Rs867228 in FPR1 accelerates the manifestation of luminal B breast cancer.","authors":"Vincent Carbonnier,&nbsp;Julie Le Naour,&nbsp;Thomas Bachelot,&nbsp;Erika Vacchelli,&nbsp;Fabrice André,&nbsp;Suzette Delaloge,&nbsp;Guido Kroemer","doi":"10.1080/2162402X.2023.2189823","DOIUrl":"https://doi.org/10.1080/2162402X.2023.2189823","url":null,"abstract":"<p><p>Formyl peptide receptor-1 (FPR1) is a pathogen recognition receptor involved in the detection of bacteria, in the control of inflammation, as well as in cancer immunosurveillance. A single nucleotide polymorphism in <i>FPR1</i>, rs867228, provokes a loss-of-function phenotype. In a bioinformatic study performed on The Cancer Genome Atlas (TCGA), we observed that homo-or heterozygosity for rs867228 in <i>FPR1</i> (which affects approximately one-third of the population across continents) accelerates age at diagnosis of specific carcinomas including luminal B breast cancer by 4.9 years. To validate this finding, we genotyped 215 patients with metastatic luminal B mammary carcinomas from the SNPs To Risk of Metastasis (SToRM) cohort. The first diagnosis of luminal B breast cancer occurred at an age of 49.2 years for individuals bearing the dysfunctional TT or TG alleles (<i>n</i> = 73) and 55.5 years for patients the functional GG alleles (<i>n</i> = 141), meaning that rs867228 accelerated the age of diagnosis by 6.3 years (<i>p</i>=0.0077, Mann & Whitney). These results confirm our original observation in an independent validation cohort. We speculate that it may be useful to include the detection of rs867228 in breast cancer screening campaigns for selectively increasing the frequency and stringency of examinations starting at a relatively young age.</p>","PeriodicalId":19683,"journal":{"name":"Oncoimmunology","volume":"12 1","pages":"2189823"},"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/2a/fc/KONI_12_2189823.PMC10038022.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9342996","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}