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Viscoelastic properties of colorectal liver metastases reflect the tumour cell viability
In: Oncology |FOR 5628
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Our paper on "Viscoelastic properties of colorectal liver metastases reflect the tumour cell viability" has been accepted for publication in Journal of Translational Medicine.

Colorectal cancer is one of the third most common cancers in the world and up to 50% of the patients develop liver metastases (CRLM) within five years. To improve and personalize therapeutic strategies, new diagnostic tools are urgently needed. An improvement could be achieved by considering biomechanical tumour properties with the implementation of magnetic resonance elastography (MRE). Our main hypothesis is that ex vivo MRE combined with histological evaluation of CRLM could provide the knowledge for using tissue mechanical properties as a diagnostic marker for cell viability in tumours.

We examined 34 CRLM samples from patients who had undergone liver resection at the Charité – Universitätsmedizin Berlin, Department of Surgery. The samples were investigated with an ex vivo MRE.  We employed a frequency range from 500 Hz to 5300 Hz, with increments of 400 Hz. For histological analysis, the samples were stained with H&E for categorization by a board-certified pathologist based on their grade of regression. The radiological response was evaluated using the RECIST-criteria.

Five samples showed major response to chemotherapy, 6 samples partial response, and 23 samples showed no response. Analysis of shear wave speed c significant correlation for frequencies including 2100 Hz and above depending on the grade of regression, indicating that low cell viability in CRLM is associated with higher tumour stiffness. Analysis of frequency-independent values of the SP-model showed a more elastic-solid behaviour at low cell viability. Our results suggest that MRE can be used to characterize the biomechanical properties associated with cell viability in CRLM, showing a higher stiffness and elastic-solid behaviour with high regression. In the future, MRE could help to improve the diagnostic tools to create an individual, tailored therapy plan for patients with CRLM.

Authors are Lisa-Marie Skrip, Simon Moosburner, Peter Tang, Jing Guo, Steffen Görner, Heiko Tzschätzsch, Clarissa Hosse, Uli Fehrenbach, Alexander Arnold, Dominik Modest, Felix Krenzien, Wenzel Schöning, Thomas Malinka, Johann Pratschke, Björn Papke, Josef A. Käs, Ingolf Sack, Igor M. Sauer, and Karl H. Hillebrandt,

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Our manuscript "Depletion of donor dendritic cells ameliorates immunogenicity of both skin and hind limb transplants" has been accepted for publication in Frontiers in Immunology, section Alloimmunity and Transplantation. Authors are Muhammad Imtiaz Ashraf, Joerg Mengwasser, Anja Reutzel-Selke, Dietrich Polenz, Kirsten Führer, Steffen Lippert, Peter Tang, Edward Michaelis, Rusan Catar, Johann Pratschke, Christian Witzel, Igor M. Sauer, Stefan G. Tullius, and Barbara Kern.

Acute cellular rejection remains a significant obstacle affecting successful outcomes of organ transplantation including vascularized composite tissue allografts (VCA). Donor antigen presenting cells (APC), particularly dendritic cells (DC), orchestrate early alloimmune responses by activating recipient effector T cells. Employing a targeted approach, we investigated the impact of donor-derived conventional DC (cDC) and APC on the immunogenicity of skin and skin-containing VCA grafts, using mouse models of skin and hind limb transplantation.
By post-transplantation day 6, skin grafts demonstrated severe rejections, characterized by predominance of recipient CD4 T cells. In contrast, hind limb grafts showed moderate rejection, primarily infiltrated by CD8 T cells. While donor depletion of cDC and APC reduced frequencies, maturation, and activation of DC in all analysed tissues of skin transplant recipients, reduction in DC activities was only observed in the spleen of hind limb recipients. Donor cDC and APC depletion did not impact all lymphocyte compartments but significantly affected CD8 T cells and activated CD4 T in lymph nodes of skin recipients. Moreover, both donor APC and cDC depletion attenuated the Th17 immune response, evident by significantly reduced Th17 (CD4+IL-17+) cells in the spleen of skin recipients and reduced levels of IL-17E and lymphotoxin-α in the serum samples of both skin and hind limb recipients. In conclusion, our findings underscore the highly immunogenic nature of skin component in VCA. The depletion of donor APC and cDC mitigates the immunogenicity of skin grafts while exerting minimal impact on VCA.

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