Ahmed Basharat

Introduction: Uterine Leiomyosarcoma (LMS) is a rare uterine cancer that accounts for 1% of uterine malignancies¹. Uterine LMS primary affects the smooth muscle of the uterus and has been found to have poor prognosis². Risk factors for uterine LMS include being over the age of 35, abnormal pre-menopausal bleeding, and menopausal status, however majority of predisposing factors have not been discovered yet^1,3. Abnormal uterine bleeding, increased abdominal girth and pelvic pain are key symptoms to look for². The most accurate way to diagnosis uterine leiomyosarcoma is through MRI.². Looking into the immune microenvironment, studies show an increase in programmed death-ligand 1 (PD-L1), CD3, and CD163 expression compare to a normal cell⁴. When CD163, CD3, and PD-L1 are plotted to a Kaplan-Meier survival curve there is a correlation with overall patient survival and low expression rate⁴. CD163 has the most significance in survival rate compared to CD3 and PD-L1⁴. These findings suggest that CD163 could play a major role in uterine LMS and could possibly be a future therapeutic target⁴. Methods: Immunohistochemistry was used to evaluate the immunomicroenvironment of LMS, specifically CD163, T cells, PD-L1 and human leukocyte antigen (HLA) class 1 expression⁴. Cytokine array was used to show the changes in cytokine production between naive cells and tumor cells⁵.Human and murine CD163 expression was measured by western blow analysis⁵. Animal studies with CD163-deficient mice and wild typed were conducted⁵. pSTAT3 production was determined by using flow cytometry and confocal⁶. The toxicity for corosolic acid packaged with long circulating liposomes (CA-LCL-alphaCD163) was measured by Cell toxicity assay⁶. Results: CD163 was shown to have a correlation with tumor grade and leiomyosarcoma⁴. When CD163 is knocked out there is a reduction in IL6 and CXCL2⁵. IL6 plays a significant role in tumor development through activation of STAT3 pathway⁵. Studies have found that tumor development is hindered in CD163 knockout of mice⁵. Loss of CD163 can also lead to an increase in survival time⁵. Inhibition of CD163+ monocytes using CA-LCL-alphaCD163 was shown to block IL-6-induced STAT3 activation and shows promise as a new therapeutic agent⁶. Conclusion: Studies have found that uterine LMS cells have a higher CD163 expression than normal cells⁴. Some experiments have shown that CD163 plays a significant role in tumor growth⁵. It has also been shown that low CD163 expression correlates with improved LMS patient survival rates⁴. Therefore, drugs that target CD163, such as CA-LCL-αCD163, have potential therapeutic application⁶.

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