Investigation of HIFU-induced anti-tumor immunity in a murine tumor model

<p>Abstract</p> <p>Background</p> <p>High intensity focused ultrasound (HIFU) is an emerging non-invasive treatment modality for localized treatment of cancers. While current clinical strategies employ HIFU exclusively for thermal ablation of the target sites, biological responses associated with both thermal and mechanical damage from focused ultrasound have not been thoroughly investigated. In particular, endogenous danger signals from HIFU-damaged tumor cells may trigger the activation of dendritic cells. This response may play a critical role in a HIFU-elicited anti-tumor immune response which can be harnessed for more effective treatment.</p> <p>Methods</p> <p>Mice bearing MC-38 colon adenocarcinoma tumors were treated with thermal and mechanical HIFU exposure settings in order to independently observe HIFU-induced effects on the host's immunological response. <it>In vivo </it>dendritic cell activity was assessed along with the host's response to challenge tumor growth.</p> <p>Results</p> <p>Thermal and mechanical HIFU were found to increase CD11c+ cells 3.1-fold and 4-fold, respectively, as compared to 1.5-fold observed for DC injection alone. In addition, thermal and mechanical HIFU increased CFSE+ DC accumulation in draining lymph nodes 5-fold and 10-fold, respectively. Moreover, focused ultrasound treatments not only caused a reduction in the growth of primary tumors, with tumor volume decreasing by 85% for thermal HIFU and 43% for mechanical HIFU, but they also provided protection against subcutaneous tumor re-challenge. Further immunological assays confirmed an enhanced CTL activity and increased tumor-specific IFN-γ-secreting cells in the mice treated by focused ultrasound, with cytotoxicity induced by mechanical HIFU reaching as high as 27% at a 10:1 effector:target ratio.</p> <p>Conclusion</p> <p>These studies present initial encouraging results confirming that focused ultrasound treatment can elicit a systemic anti-tumor immune response, and they suggest that this immunity is closely related to dendritic cell activation. Because DC activation was more pronounced when tumor cells were mechanically lysed by focused ultrasound treatment, mechanical HIFU in particular may be employed as a potential strategy in combination with subsequent thermal ablations for increasing the efficacy of HIFU cancer treatment by enhancing the host's anti-tumor immunity.</p

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Investigation of HIFU-induced anti-tumor immunity in a murine tumor model-2

<p><b>Copyright information:</b></p><p>Taken from "Investigation of HIFU-induced anti-tumor immunity in a murine tumor model"</p><p>http://www.translational-medicine.com/content/5/1/34</p><p>Journal of Translational Medicine 2007;5():34-34.</p><p>Published online 11 Jul 2007</p><p>PMCID:PMC1939831.</p><p></p>llected 1–2 days after HIFU treatment. 6-μm cryostat sections were cut and stained with anti-CD11c Abs. Then the antibody was visualized using the Anti-Hamster Ig HRP detection kit. The sections were counterstained with hematoxylin

Investigation of HIFU-induced anti-tumor immunity in a murine tumor model-5

<p><b>Copyright information:</b></p><p>Taken from "Investigation of HIFU-induced anti-tumor immunity in a murine tumor model"</p><p>http://www.translational-medicine.com/content/5/1/34</p><p>Journal of Translational Medicine 2007;5():34-34.</p><p>Published online 11 Jul 2007</p><p>PMCID:PMC1939831.</p><p></p>cavitation detection (PCD) signals, and (C) images of tumor tissue injury produced by different HIFU treatment

Investigation of HIFU-induced anti-tumor immunity in a murine tumor model-0

<p><b>Copyright information:</b></p><p>Taken from "Investigation of HIFU-induced anti-tumor immunity in a murine tumor model"</p><p>http://www.translational-medicine.com/content/5/1/34</p><p>Journal of Translational Medicine 2007;5():34-34.</p><p>Published online 11 Jul 2007</p><p>PMCID:PMC1939831.</p><p></p>cavitation detection (PCD) signals, and (C) images of tumor tissue injury produced by different HIFU treatment

Investigation of HIFU-induced anti-tumor immunity in a murine tumor model-4

<p><b>Copyright information:</b></p><p>Taken from "Investigation of HIFU-induced anti-tumor immunity in a murine tumor model"</p><p>http://www.translational-medicine.com/content/5/1/34</p><p>Journal of Translational Medicine 2007;5():34-34.</p><p>Published online 11 Jul 2007</p><p>PMCID:PMC1939831.</p><p></p>ors, and induced tumor-specific CTL response (C), and IFN-γ-secreting cells (D) in the spleens of treated mice. C57BL/6 mice were inoculated s.c. on right hind leg with 5 × 10MC38 tumor cells and treated with different HIFU on day 9 of tumor inoculation. Mice were challenged with 1 × 10MC38 tumor cells by s.c. inoculation on the left hind leg one day after HIFU treatment. Both primary and challenged tumor growth were monitored daily. Splenocytes obtained from control and treated mice 10 days after HIFU treatment were re-stimulated with mytomicin-pretreated MC-38 or EL4 tumor cells and CTL and ELISPOTS assays were performed. Results were expressed as mean value ± SD for each group (n = 8). *P < 0.05; **P < 0.001 versus non-treatment control. This experiment is representative of three experiments with consistent results

Investigation of HIFU-induced anti-tumor immunity in a murine tumor model-3

<p><b>Copyright information:</b></p><p>Taken from "Investigation of HIFU-induced anti-tumor immunity in a murine tumor model"</p><p>http://www.translational-medicine.com/content/5/1/34</p><p>Journal of Translational Medicine 2007;5():34-34.</p><p>Published online 11 Jul 2007</p><p>PMCID:PMC1939831.</p><p></p>FSE-labeled immature bone marrow-derived DCs were injected into tumor 1 day after HIFU treatment. The (A) total cell number, (B) total number of DC(CD11ccells), and (C) migrating DC (CFSECD11ccells) recovered in DLN on day 2 were determined by flow cytometry. Data points represent the mean ± SD for each group (n = 8). *P < 0.05 versus DC injection only control group. (D) Representative histogram illustrating the population of CFSECD11ccells within the DLN of mice subjected to different treatments

Investigation of HIFU-induced anti-tumor immunity in a murine tumor model-1

<p><b>Copyright information:</b></p><p>Taken from "Investigation of HIFU-induced anti-tumor immunity in a murine tumor model"</p><p>http://www.translational-medicine.com/content/5/1/34</p><p>Journal of Translational Medicine 2007;5():34-34.</p><p>Published online 11 Jul 2007</p><p>PMCID:PMC1939831.</p><p></p>ing. Bright hyperechoic spots generated by HIFU indicate regions of cavitation