On June 20, 2023 Vizgen, the life science company dedicated to improving human health by visualizing single-cell spatial genomics information, reported publication of a study in the June issue of Nature Medicine conducted by Drs. Assaf Magen and Pauline Hamon in the Miriam Merad lab at the Icahn School of Medicine at Mount Sinai, in collaboration with Regeneron Pharmaceuticals, Inc (Press release, Vizgen, JUN 20, 2023, View Source [SID1234632814]). The spatial characterization described in this study was enabled by the company’s spatial transcriptomics MERSCOPE Platform, which simplifies and empowers the entire workflow from sample preparation through data visualization.
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The study, "Intratumoral dendritic cell–CD4+ T helper cell niches enable CD8+ T cell differentiation following PD-1 blockade in hepatocellular carcinoma," leveraged a large neoadjuvant PD-1 blockade trial in patients with hepatocellular carcinoma (HCC) to search for correlates of response to immune checkpoint blockade (ICB) within T-cell rich tumors. Integration of single-cell RNA and TCR sequencing, together with several imaging approaches suggested that T cell activation and expansion occurs predominately at the tumor site and is promoted by CXCL13+ CD4 T cells and mregDCs (mature dendritic cells that have captured tumor antigens). These data provide the closest cellular resolution of T cell diversity in PD-1 treated patients seen in HCC. These findings could be used to develop new therapies targeting these cellular triads.
"Vizgen was developed precisely for the type of work conducted in this study and it is immensely gratifying to see our spatial transcriptomics platform play an important role in evaluating and imaging gene panels and in understanding cellular role and function in this clinical trial, which could ultimately improve tumor response to treatment," said Terry Lo, President and CEO of Vizgen. "We look forward to the continued demonstration of Vizgen’s multiplexing, high resolution in situ MERSCOPE Platform’s potential in empowering future breakthrough biological discoveries."
Surgical resection is traditionally the preferred treatment for HCC, a rare, aggressive type of liver cancer that is only variably responsive to chemotherapy, and more than half of these tumors recur within 2 years. Neoadjuvant immune checkpoint blockade targeting the PD-1/PD-L1 axis has been successful in inducing pathological response and preventing recurrence in multiple tumor types, in part by driving the expansion of tumor-specific T cells, which may also induce systemic immunity and eliminate micrometastases. This neoadjuvant clinical trial for early-stage HCC patients, led by Drs. Thomas Marron and Myron Schwartz, in which treatment-naive patients received two doses of PD-1 blockade prior to surgery, observed a 30% pathological response rate, which prompted a more detailed investigation into the cellular and molecular pathways that promote an effective anti-tumor immune response.
"I am excited about the high quality of the data produced by this study and the important implications this has for HCC and cancer biology as a whole," said Jiang He, PhD, Scientific Co-founder and Senior Director of Scientific Affairs of Vizgen. "We hypothesize that this interaction between mregDCs, helper cells and T cells could be critical across multiple other cancers. We hope this is the first of many discoveries driving insight into PD-1 therapy and advancing our treatment of cancer patients."