Publications by authors named "Anne-Gaelle Goubet"
Secreted phosphosprotein 1 (SPP1) tumor-associated macrophages (TAM) are abundant tumor myeloid cells that are immunosuppressive, pro-tumorigenic, and have a highly negative prognostic factor. Despite this, there is a lack of efficient TAM-specific therapeutics capable of reducing SPP1 expression. Here, on a phenotypic screen is reported to identify small molecule SPP1 modulators in macrophages.
View Article and Find Full Text PDFTumor-associated macrophages (TAM) are a diverse population of myeloid cells that are often abundant and immunosuppressive in human cancers. CXCL9 TAM has recently been described to have an antitumor phenotype and is linked to immune checkpoint response. Despite the emerging understanding of the unique antitumor TAM phenotype, there is a lack of TAM-specific therapeutics to exploit this new biological understanding.
View Article and Find Full Text PDFArticle Synopsis
- - The introduction of immune checkpoint blockers (ICBs) has significantly improved the treatment of advanced cancers in the urinary tract by enhancing the body's immune response against tumors.
- - Immunogenic cancers, characterized by high mutation rates and specific immune cell infiltrates, respond better to immunotherapy, and ongoing research aims to identify effective tumor antigens and natural immune boosters.
- - The presence of certain bacteria in the urinary tract can influence treatment outcomes and immune responses, suggesting that manipulating these bacteria could lead to improved cancer treatments when combined with ICBs.
Microorganisms have been identified in tumor specimens for over a century. It is only in recent years that tumor-associated microbiota has become a rapidly expanding field. Assessment techniques encompass methods at the frontiers of molecular biology, microbiology, and histology, requiring a transdisciplinary process to carefully decipher this new component of the tumor microenvironment.
View Article and Find Full Text PDFArticle Synopsis
- Recent studies indicate that combining cancer immunotherapy drugs can improve survival rates for patients with advanced mesothelioma who respond to treatment.
- A trial involving pembrolizumab and nintedanib revealed that patients resistant to these treatments had active immune responses, but also exhibited genetic alterations linked to inflammation and immune suppression in their tumors.
- Findings suggest that understanding the specific tumor biology of mesothelioma could lead to more effective, tailored combination therapies for better patient outcomes.
Article Synopsis
- - Biomarkers are necessary to optimize the use of immune-checkpoint blockers (ICB) like pembrolizumab for patients with localized muscle-invasive bladder cancer (MIBC), as highlighted by the study on T cells and immune responses.
- - The research identified follicular helper CD4+ T cells (TFH) and specific antibodies against E. coli as potential biomarkers that correlate with better clinical outcomes for patients receiving pembrolizumab treatment.
- - Understanding the connections between tumor infections and immune responses can lead to improved therapeutic strategies and better patient management in the future.
Article Synopsis
- * Research revealed two patterns of immune response: one with reduced HLA-I expression linked to a suppressive tumor environment and poor prognosis, and another with preserved HLA-I that showed signs of effective immune activity and better outcomes.
- * The study suggests that HLA-I expression at relapse is a result of immune subversion initiated by BCG, rather than just a consequence of immune editing, highlighting the importance of HLA-I testing for guiding treatment options.
Article Synopsis
- Prostate cancer typically progresses from hormone-sensitive forms to castration-resistant forms despite androgen deprivation therapy (ADT), prompting research into the role of T lymphocytes and gut microbiota in treatment effectiveness.
- In mouse models, ADT improved thymic function and was less effective in mice lacking T lymphocytes or with depleted gut microbiota, showing connections between immune response and therapy outcomes.
- Analysis of prostate cancer patients indicated that long-term ADT increased immune cell output and altered gut microbiota, with the potential for fecal transplants from healthy donors to improve treatment response, highlighting the need for addressing intestinal health in therapy.
Article Synopsis
- The study investigates how memory T cells respond to the SARS-CoV-2 virus and its variants, focusing on their link to protection against COVID-19 in healthy and cancer patients.
- Findings suggest that an imbalance in immune responses, particularly between type 1 and type 2 cytokines, increases vulnerability to the virus, especially in individuals with specific deficiencies in T helper 1 (Th1) cells.
- Current vaccines primarily trigger Th1 responses effectively against the original virus strain, highlighting the need for future vaccines to target T-cell responses against the receptor binding domain of new variants.
Article Synopsis
- Gut dysbiosis is linked to both intestinal and extraintestinal cancers; however, the relationship between cancer development and changes in the microbiome is still unclear.
- The study found that cancer can cause damage to the ileal mucosa, leading to changes in gut permeability and a rise in Clostridium species, which are associated with dysbiosis.
- Interventions like β-adrenergic receptor blockers or antibiotics helped prevent the detrimental gut changes linked to tumors, suggesting stress ileopathy is an important condition in cancer that needs targeted treatment.
Article Synopsis
- * Analysis found significant changes in 77 metabolites (like amino acids and sugars) in critical COVID-19 patients compared to those with mild symptoms.
- * Among moderately ill patients treated with tocilizumab, only 10 metabolites differed in those who improved versus those who worsened, with high levels of anthranilic acid linked to poor outcomes, suggesting potential therapeutic targets for treatment.
Article Synopsis
- Decision making in immuno-oncology relies on adapting therapies to the tumor microenvironment (TME), but predicting the optimal combination of treatments remains a challenge.
- A new multiplex functional and dynamic immuno-assay was developed to assess how 43 human primary tumors respond to 12 different immunomodulators, including immune checkpoint inhibitors (ICI).
- This “in sitro” assay shows promise in predicting which tumors might not respond to anti-PD-1 monoclonal antibodies and in identifying personalized treatment combinations, but further clinical trials are needed to confirm its efficacy.
Over the past 16 years, three coronaviruses (CoVs), severe acute respiratory syndrome CoV (SARS-CoV) in 2002, Middle East respiratory syndrome CoV (MERS-CoV) in 2012 and 2015, and SARS-CoV-2 in 2020, have been causing severe and fatal human epidemics. The unpredictability of coronavirus disease-19 (COVID-19) poses a major burden on health care and economic systems across the world. This is caused by the paucity of in-depth knowledge of the risk factors for severe COVID-19, insufficient diagnostic tools for the detection of SARS-CoV-2, as well as the absence of specific and effective drug treatments.
View Article and Find Full Text PDFIntestinal microbiota have been proposed to induce commensal-specific memory T cells that cross-react with tumor-associated antigens. We identified major histocompatibility complex (MHC) class I-binding epitopes in the tail length tape measure protein (TMP) of a prophage found in the genome of the bacteriophage Mice bearing harboring this prophage mounted a TMP-specific H-2K-restricted CD8 T lymphocyte response upon immunotherapy with cyclophosphamide or anti-PD-1 antibodies. Administration of bacterial strains engineered to express the TMP epitope improved immunotherapy in mice.
View Article and Find Full Text PDFArticle Synopsis
- Blood myeloid cells show dysregulation in COVID-19, with changes in monocyte and neutrophil populations linked to disease severity.
- In severe cases, there's a notable decrease in non-classical CD14CD16 monocytes and an accumulation of HLA-DR classical monocytes, along with high levels of calprotectin.
- The findings suggest that measuring calprotectin levels and non-classical monocyte frequencies could help predict which COVID-19 patients are at higher risk for severe illness, indicating a need for further study.
Article Synopsis
- The study investigates how the composition of stool bacteria in kidney cancer patients affects the effectiveness of immune checkpoint blockade (ICB) therapy, specifically nivolumab, which has been shown to improve treatment outcomes in renal cell carcinoma (RCC).
- Researchers collected fecal samples from 69 advanced RCC patients and analyzed these alongside samples from healthy volunteers to find correlations between gut bacteria and treatment responses, while also examining the impact of antibiotics and tyrosine kinase inhibitors on microbiota.
- The findings suggest that recent antibiotic use significantly reduces response rates to ICB therapy, emphasizing the importance of gut bacteria in predicting patient outcomes and highlighting a potential area for improving cancer treatment strategies.
Mucosal-associated invariant T (MAIT) cells are abundant T cells with unique specificity for microbial metabolites. MAIT conservation along evolution indicates important functions, but their low frequency in mice has hampered their detailed characterization. Here, we performed the first transcriptomic analysis of murine MAIT cells.
View Article and Find Full Text PDF