Publications by authors named "Alexei Hernandez"
Article Synopsis
- * In a Phase II clinical trial, 27 patients received entinostat followed by nivolumab, resulting in an objective response rate of 11% and a median response duration of over 10 months, although the primary endpoint for overall effectiveness was not reached.
- * The combination treatment led to significant immune profile changes, including increased dendritic cell activity and enhanced inflammatory response, suggesting potential for improving treatment strategies in PDA despite
Tertiary lymphoid structures (TLS) are associated with improved response in solid tumors treated with immune checkpoint blockade, but understanding of the prognostic and predictive value of TLS and the circumstances of their resolution is incomplete. Here we show that in hepatocellular carcinoma treated with neoadjuvant immunotherapy, high intratumoral TLS density at the time of surgery is associated with pathologic response and improved relapse-free survival. In areas of tumor regression, we identify a noncanonical involuted morphology of TLS marked by dispersion of the B cell follicle, persistence of a T cell zone enriched for T cell-mature dendritic cell interactions and increased expression of T cell memory markers.
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- Immune-related adverse events (irAEs) pose significant risks for patients receiving immune checkpoint inhibitors (ICIs), highlighting the need to identify patients at higher risk and develop strategies to manage these complications.
- An observational study involving 111 patients found that 40.5% experienced symptomatic irAEs, with higher rates linked to combination ICI therapy and pre-existing autoimmune disorders.
- Early increases in specific cytokines and T helper cell populations were associated with developing severe irAEs, indicating potential biomarkers for monitoring and targeting therapeutic interventions.
Article Synopsis
- Metastasis is a big reason why many people die from cancer, and this study found specific cancer cells that help it spread.
- The researchers looked at how these cancer cells interact with other cells in their environment using a special imaging technique.
- They discovered that the cancer cells that cause metastasis are often found close to certain types of immune and connective tissue cells, which might help them spread even more.
Article Synopsis
- Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer that resists immunotherapy, largely due to an immunosuppressive environment created by myeloid cells.
- A combination of the PDE5 inhibitor tadalafil with a specific vaccine and immune checkpoint inhibitors shows promise in enhancing the immune response against PDAC, even in cases previously deemed immune-resistant.
- Tadalafil helps reprogram myeloid cells to reduce their suppression of T cells, leading to improved T cell activation and pro-inflammatory signaling, which boosts anti-tumor effects.
Article Synopsis
- * This study uses spatial imaging mass cytometry to investigate PN skin, revealing increased levels of inflammatory markers and specific types of immune cells in lesional skin compared to healthy skin.
- * The research suggests that certain macrophages in PN may play a significant role in causing itchiness, indicating a complex interaction between skin cells and immune cells, which could influence future treatments for the condition.
Article Synopsis
- - The study involved 24 women with breast cancer, split evenly between hormone receptor-positive and advanced triple-negative types, treated with a combination of entinostat, nivolumab, and ipilimumab.
- - Results showed no severe side effects and indicated a 25% overall response rate, with better outcomes (40%) in triple-negative patients compared to hormone receptor-positive (10%).
- - The treatment yielded a 40% clinical benefit rate and a 50% progression-free survival rate at 6 months, suggesting further research in a phase II trial is warranted.
Microbes are an integral component of the tumor microenvironment. However, determinants of microbial presence remain ill-defined. Here, using spatial-profiling technologies, we show that bacterial and immune cell heterogeneity are spatially coupled.
View Article and Find Full Text PDFIntrahepatic cholangiocarcinoma (ICC) has limited therapeutic options and a dismal prognosis. Adding blockade of the anti-programmed cell death protein (PD)-1 pathway to gemcitabine/cisplatin chemotherapy has recently shown efficacy in biliary tract cancers but with low response rates. Here, we studied the effects of anti-cytotoxic T lymphocyte antigen (CTLA)-4 when combined with anti-PD-1 and gemcitabine/cisplatin in orthotopic murine models of ICC.
View Article and Find Full Text PDFThe addition of anti-VEGF antibody treatment to immune checkpoint blockade (ICB) has increased the efficacy of immunotherapy in advanced hepatocellular carcinoma (HCC). Despite an initial promise, adding multitargeted kinase inhibitors of VEGFR with ICB has failed to increase survival in HCC. To reveal the mechanisms underlying treatment failure, we studied the effects of cabozantinib/ICB using orthotopic murine HCC models with or without liver damage.
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- Neoadjuvant immunotherapy may help achieve long-term tumor remission by boosting the body's immune responses before tumor removal, and this study explores the role of tertiary lymphoid structures (TLS) in this process for liver cancer (HCC).
- The research found that neoadjuvant immunotherapy not only promotes the formation of TLS but also correlates with better treatment outcomes, including higher levels of T and B cells and improved disease-free survival.
- Notably, the study observed that as tumors regress, TLS undergo changes that indicate continued immune activity and contribute to T cell memory, which may be crucial for long-term immunity against cancer.
Purpose: Pembrolizumab significantly improves clinical outcomes in advanced/metastatic microsatellite instability high (MSI-H)/deficient mismatch repair (dMMR) solid tumors but is not well studied in the neoadjuvant space.
Methods: This is a phase II open-label, single-center trial of localized unresectable or high-risk resectable MSI-H/dMMR tumors. Treatment is pembrolizumab 200 mg once every 3 weeks for 6 months followed by surgical resection with an option to continue therapy for 1 year followed by observation.
Techniques for robust immune profiling of mouse tumor and blood are key to understanding immunological responses in mouse models of cancer. Here, we describe mass cytometry (cytometry by time-of-flight) procedures to facilitate high-parameter profiling of low-volume survival blood samples and end-of-study tumor samples. We employ live-cell barcoding systems to mark all cells from each tumor and blood to improve cost-effectiveness and minimize batch effects.
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- * Researchers are using advanced techniques like imaging mass cytometry to analyze immune tumor microenvironments in different mouse HCC models, finding significant variations in immune profiles and pathways among them.
- * The study highlights the necessity of using multiple syngeneic mouse models to gain a better understanding of the immune mechanisms involved in HCC, which may ultimately enhance treatment strategies through immune modulation.