April 8–13, 2022 | New Orleans, LA
Every year, the AACR Annual Meeting is an enormous event featuring insights into ground-breaking developments and advancements in cancer research. This year, we are pleased to contribute to the meeting with our Spotlight Theater, presenting two scientific talks on how cancer researchers use single-cell sequencing and high-content imaging to drive the identification of biomarkers in the tumor microenvironment (TME).
We are thrilled to finally meet you in person again, and we’re looking forward to welcoming you to our booth. Drop by and be inspired by our whole workflow solutions, which include solid tumor dissociation, cell isolation, cell analysis and cell culture, as well as ultrahigh-content imaging and light sheet microscopy.
Your thoughts count – visit us at our booth to complete our survey and we will plant a tree on your behalf. Fill out our short questionnaire, and you may also win one of our daily exciting prizes.
Join our spotlight theater and gain valuable insight into how our technologies unravel the complexity of the tumor microenvironment, enabling high-quality multiomics analysis to improve cancer immunotherapy. You will find out which state-of-the-art imaging approaches can defy TME complexity.
Speaker: Prof. Abhishek D. Garg, KU Leuven, Belgium
Tumour-infiltrating CD8+T cells exhibit exhausted or dysfunctional-states, but their clinico-immunological or malignancy-dependent biomarkers remain disputed. Using multiomics mapping integrating multiple patient-cohorts, at bulk- and single-cell levels, we identified a continuum of CD8+T cell population-states across tumour/organ-specific immune-niches, largely subclassifying as differentially exhausted CD8+T cells (enriched in immune-supportive tumours) or severely-dysfunctional CD8+T cells (enriched in immune-refractory tumours).
We validated these CD8+T cell states’ multiomics characteristics (transcriptomic/proteomic on bulk-tumour or single-cell levels), spatial features (transcriptomic/proteomic on bulk-anatomic or single-cell levels), as well as functional profiles (TCR assays, immunophenotyping and single-cell secretome). We also established a high relevance of these CD8+T cell-states as prognostic or predictive features in human immuno-oncology clinical trials administering various immune-checkpoint blockers (anti-PD1, anti-PDL1 or anti-CTLA4 mAbs) or cellular immunotherapies (DC vaccines or ACT). Collectively, in this study, we provide an atlas of immunodynamic biomarkers and computational resources for assessing differential CD8+T cell population-states and differential clinical immunotherapy-responses.
Prof. Abhishek D. Garg is the Assistant Professor at KU Leuven, Belgium, and the Head of the Cell Stress & Immunity Lab. He has several years of experience in cellular and molecular immunology, cancer cell death and stress response-related immunology, cancer immunology, and immunotherapy. During his PhD he performed front-line research on damage-associated molecular patterns and immunogenic cell death (ICD) in cancer, and pursued studies on various immunological determinants of ICD and ICD-based DC vaccines as a postdoctoral researcher. He has also carried out international research visits to work on different aspects of cancer cell-innate immune cell interface and the interaction of antigen-specific T cells with cancer cells. As head of the CSI Lab, Prof. Garg is aiming to effectively bridge the glaring gap between clinical and preclinical evidence via reserve translational approaches, to facilitate translational immuno-oncology.
Speaker: Dr. Rita Pfeifer, Miltenyi Biotec
One major drawback in the field of CAR T cell therapy in solid tumors is the lack of spatiotemporal information that enables monitoring of T cell localization, biodistribution, and activation status. To address this challenge, we combined 3D µCT bioluminescence tomography (BLT), light-sheet fluorescence microscopy (LSFM), and cyclic immunofluorescence staining (MACSima™).
Intratumoral CAR T cell trafficking was monitored in a subcutaneous pancreatic cancer xenograft mouse model over time. Accumulation of CAR T cell in tumor tissue, based on target-dependent infiltration, was significantly increased in comparison to target-independent infiltration as quantified by 3D µCT/BLT. These findings were confirmed by ex-vivo LSFM 3D quantitative analysis, revealing deeper T cell tumor infiltration for the target-positive cohort. MACSima™ revealed that local IL-2 application resulted in intratumoral T cell exhaustion. Overall, these results demonstrate that optical tomography-based in-vivo CAR T cell whole-body tracking and ex-vivo 3D- and sequential 2D-microscopy analysis are valuable tools to assess T cell infiltration and status within tumor tissue.
Dr. Rita Pfeifer studied Biochemistry at the University of Tübingen, Germany, followed by a position as Research Fellow at the Children’s Hospital Los Angeles, USA. Thereafter, she returned to Germany to start her Ph.D. at the University of Tübingen and Miltenyi Biotec. Since 2018, she has continued her work with Miltenyi Biotec as Team Coordinator Research and Development, focusing on in-vivo and ex-vivo tracking, and the development of CAR T cell therapies against solid tumors.
As in previous years, we have also submitted a few of our own scientific posters – check them out, and come along for the discussion.
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