ESTRO 2021 Abstract Book


ESTRO 2021

Conclusion We have shown that direct QoL-guided plan optimisation is feasible, improves expected QoL, and facilitates planning process automation. In the current implementation human interaction is still needed to tune target coverage, hot spots, and dose conformity, but adding models for these clinical goals in relation to QoL would render the process fully automated. Moreover, the automation is not based on mimicking human planning (such as with AI solutions) but on modelling of historic patient data, which can be continuously updated in a closed rapid learning healthcare loop. This process translates observed outcomes directly and objectively into optimal planning strategies whereas conventionally this process involves subjective human interpretation or historic habits. Future developments are needed to support more generic models with less scripting and C++ programming and to allow non-convex objective functions. OC-0182 SIRT2 promotes murine melanoma progression through natural killer cell inhibition S. Acklin-Wehnert 1 , M. Zhang 2 , J. Gillenwater 2 , W. Du 2 , M. Patra 2 , J. Yu 3 , F. Xia 2 1 Duke University, Department of Radiation Oncology, Durham, USA; 2 University of Arkansas for Medical Sciences, Department of Radiation Oncology, Little Rock, USA; 3 City of Hope, Department of Hematology & Hematopoietic Cell Transplantation, Duarte, USA Purpose or Objective SIRT2, an NAD + -dependent histone deacetylase, has been shown to play a pivotal role in various physiological processes, however, its role in cancer is currently controversial. In recent years, SIRT2 has been described as both a tumor suppressor and oncogene with divergent expression and function in various malignancies. With established roles in inflammation and glucose and iron metabolism, systemic and microenvironment SIRT2, rather than just intrinsic tumor cell expression, might have implications in tumor progression. Moreover, recent interest in the tumor immune microenvironment has further characterized immune cells involved in tumor suppression, including natural killer (NK) cells. Here, we sought to investigate the biological role of systemic SIRT2 in melanoma tumor progression and to evaluate its interaction with key tumor suppressive immune cells. Materials and Methods Murine models were employed to investigate the effect of systemic SIRT2 on melanoma tumor progression. Tumor progression was measured in terms of weight and volume for 20 days following subcutaneous inoculation of Sirt2 -KI and WT mice with B16-F10 melanoma cells. Differences in tumor-infiltrating immune cell composition were determined by flow cytometry. Granzyme B and Ki-67 immunohistochemical staining was used to measure NK cell functional activity and proliferation in in vivo melanoma samples. NK cell function was further evaluated using in vitro and ex vivo mouse models as well as an in vitro human model. Antibody-mediated NK cell depletion established NK cells as an integral player in SIRT2-mediated tumor promotion. Finally, SIRT2 was pharmacologically inhibited by SirReal2, and the effect on melanoma progression and NK cell tumor infiltration was established. Results Increased systemic expression of SIRT2 promoted melanoma progression in mice, resulting in larger and heavier tumors. Mechanistically, systemic SIRT2 overexpression reduced the number of tumor-infiltrating NK cells and suppressed NK cell activation and proliferation within the tumor microenvironment. Furthermore, despite the effect of increased tumor growth rate and tumor volume in wild-type littermate mice, NK cell Proffered papers: Proffered Papers 9: Radiation immune effects

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