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Sandra Cascio, PhD
Assistant Professor, Department of OBGYN-Reproductive Sciences, Magee-Womens Research Institute
“Only 10-15% of ovarian cancer patients respond to current immune checkpoint inhibitors. My research aims to develop novel immune therapies by reprogramming dysfunctional myeloid cells within the tumor microenvironment to enhance T and NK cell -mediated tumor killing activities and suppress tumor growth”.
Sandra Cascio, PhD
Research in Brief
The Cascio’s Lab investigates the intercellular communications between stroma, tumor cells and immune cells within the tumor microenvironment. Our studies focus on gaining a better understanding of how factors, secreted by stromal and tumor cells, modulate the immunosuppressive activities of tumor-associated myeloid cells, driving resistance to immunotherapies. Using mouse models of ovarian cancer and clinical samples, our long-term goal is to identify novel therapeutical approaches to enhance anti-tumor immunity.
Current Projects
The role of tumor EGFL6 in tumor immunity
Link between ovarian cancer, microbiome and myeloid cells
Intercellular communication between myeloid cells and stromal cells in the ovarian tumor microenvironment
Selected Publications
1) S Hamze Sinno, JA Imperatore, S Bai, N Gomes-Jourdan, N Mafarachisi, C Coronnello, L Zhang, E Jašarević, HU Osmanbeyoglu, RJ Buckanovich, S Cascio. Egfl6 promotes ovarian cancer progression by enhancing the immunosuppressive functions of tumor-associated myeloid cells. J Clin Invest. 2024 Nov 1;134(21):e175147. doi: 10.1172/JCI175147.PMID: 39312740
2) L Zhang#, S Cascio#, C Adams, J W Mellors, R J Buckanovich, H U Osmanbeyoglu. Singlecell analysis reveals the stromal dynamics and tumor-specific characteristics in the microenvironment of ovarian cancer. (#Contributed equally). Communications Biology; 2024 Jan 5;7(1):20. doi: 10.1038/s42003-023-05733-x.
3) Cascio S, Chandler C, Zhang L, Sinno S, Gao B, Onkar S, Bruno TC, Vignali DAA, Mahdi H, Osmanbeyoglu HU, Vlad AM, Coffman LG, Buckanovich RJ. Cancer-associated MSC drive tumor immune exclusion and resistance to immunotherapy, which can be overcome by Hedgehog inhibition. Sci Adv. 2021 Nov 12;7(46):eabi5790. doi: 10.1126/sciadv.abi5790. Epub 2021 Nov 12. PMID: 34767446
4) Kvorjak M, Ahmed Y, Miller LM, Sriram R, Coronello C, Hashash GJ, Hartman JD, Telmer AC, Miskov-Zinavov N, Finn JO and Cascio S. Crosstalk between Colon Cells and Macrophages Increases ST6GALNAC1 and MUC1-sTn Expression in Ulcerative Colitis and Colitis-Associated Colon Cancer. Cancer Immunology Research. 2020 Feb;8(2):167-178. doi: 10.1158/2326-6066.
5) Cascio S, Faylo JL, Sciurba JC, Xu J, Ranganathan S, Lohmueller JJ, Beatty PL and Finn OJ. Abnormally glycosylated MUC1 establishes a positive feedback circuit of inflammatory cytokines, mediated by NF-kB p65 and EzH2, in colitis-associated cancer. Oncotarget. 2017 https://doi.org/10.18632/oncotarget.22168
6) Cascio S, Medsger TA Jr, Hawse WF, Watkins SC, Milcarek C, Moreland LW, Lafyatis RA, Fuschiotti P. 14-3-3z sequesters cytosolic T-bet, up-regulating IL-13 in Tc2 and scleroderma CD8+ lymphocytes. J Allergy Clin Immunol. 2017 Nov 15. pii: S0091-6749(17)31760-8. doi: 10.1016/j.jaci.2017.10.029