2021 Recipient — Sandra Cascio, PhD

Dr. Sandra Cascio

Sandra Cascio, PhD

EGFL6 as a New Regulator of Myeloid Cell Expansion and Function in HGSOC

Project Summary

Ovarian cancer (OvCa) is the deadliest US gynecologic malignancy with a clear need for novel therapeutic approaches. Immunotherapy, a class of treatments that restores the patient’s immune system to recognize and kill cancer cells, is one promising approach to improve the outcome of OvCa patients. While current immune therapies work very well in some types of cancer, they show limited clinical efficacy in women with ovarian cancer with response rates of 10–15%.

One reason for these disappointing results may be OvCa’s unique tumor microenvironment (TME). The ovarian TME is characterized by large numbers of immune suppressor cells that inactivate the cancer fighting immune cells and inhibit the response of current immune therapy treatments. Despite this there are currently no approved therapies for targeting immune suppressor cells in the OvCa TME. We have discovered that EGFL6, a protein secreted by OvCa cells, induces tumor growth and drives an accumulation of immune suppressor cells in the tumor. We hypothesize that blocking EGFL6 will be an important therapeutic approach to prevent immune suppressor from entering the tumor and thereby enhance the efficacy of anti-tumor immune therapies. To test our hypothesis, we propose the following aims:

Specific Aim (1) To determine the molecular mechanisms by which EGFL6 controls proliferation, migration and differentiation of immune suppressor cells,
Specific Aim (2) To determine the immune-suppressive functions of EGFL6 within the tumor of mouse and human OvCa ascites and tumor tissues and
Specific Aim (3) To determine if therapeutics targeting EGFL6 will restore an active anti-tumor immune response. We will also determine if EGFL6 targeting therapy will act as an adjuvant to current immune therapeutic approaches.
IMPACT: These studies will evaluate a critical new target to enhance immune therapy. If successful, our studies could be translated into the clinic to improve the long-term survival of women with OvC.


Dr. Sandra Cascio is a Research Assistant Professor at the Magee-Womens Research Institute and the University of Pittsburgh's Department of OBGYN and Reproductive Sciences. She has received several prestigious national and international awards including the Ri.MED Foundation Grant, AIRC Fellowship, AACR-Scholar-in-Training Award and the Competitive Medical Research Fund Grant. Dr. Cascio obtained her PhD in Molecular Oncology from the University of Palermo (Italy) performing her thesis at Thomas Jefferson University (Philadelphia, PA) as Visiting Scholar. She studied the link between obesity and cancer, elucidating novel signaling pathways of leptin in breast and colon adenocarcinoma. During her post-doctoral training in the laboratory of Dr. Olivera Finn at the University of Pittsburgh she acquired expertise in tumor immunology developing a project focused on the crosstalk between tumor-associated macrophages and tumor epithelial cells. In 2019, Dr. Cascio joined Dr. Buckanovich’ group to study the cellular and molecular networks in the ovarian tumor microenvironment. Her research interests are centered on the molecular mechanisms that drive proliferation and differentiation of immunosuppressive myeloid cells and develop new strategies that will improve the efficacy of current immune checkpoint therapies in ovarian cancer.

Researcher Spotlight: Meet a Scientist

Dr. Sandra Cascio of Magee-Womens Research Institute is a 2021 recipient of OCRA's Early Career Investigative Grant. With her project, "EGFL6 as a New Regulator of Myeloid Cell Expansion and Function in HGSOC," Dr. Cascio seeks to better understand ovarian tumors' microenvironments and, ultimately, to overcome ovarian cancer resistance to immunotherapy, opening up a new and effective avenue for treatment.

What initially sparked your interest in science?

Dr. Sandra Cascio outdoors

My interest in science began during my years in high school when I studied cell-cell communications. I was fascinated by the sophisticated and complex mechanisms by which one cell influences the behavior of another and by the fact that wrong signals between cells could cause serious tissue dysfunctions.

What drew you to the field of ovarian cancer research?

Ovarian cancer is highly metastatic with a very low survival rate. As a scientist and human being, I really hope to see this aggressive disease transformed into a curable disease so that ovarian cancer patients will suffer less and live longer. I recently joined an amazing team of researchers and clinicians at the Magee-Womens Research Institute, and I am confident we will make significant advances against ovarian cancer.

Can you explain your research project?

The ovarian tumor microenvironment is composed of a variety of cells, including tumor, stromal and immune cells. Tumor cells recruit immune cells, including macrophages, into the tumors and program them to have pro-tumor behavior. In turn, tumor-infiltrating macrophages can turn off the tumor-killing activities of other immune cell types, named T and NK cells. All these events drive tumor progression, metastasis, and immunotherapy resistance. I am currently focused on understanding the intercellular network that drives resistance to immunotherapy. The goal of my research is to develop new therapeutic strategies that will target immunosuppressive macrophages and allow the cancer-fighting immune cells to eliminate cancer completely.

What motivates you to persist in your research?

I have friends who are cancer survivors and are completely cured. With my work, I hope to see more survivors able to enjoy their life without the fear of cancer recurrence.

What is your hope for the field of ovarian cancer research?

I hope we will better understand why ovarian cancer patients respond poorly to immunotherapy and develop new therapeutic approaches that will improve the efficacy of current immunotherapy.

If you had the opportunity to personally thank someone from the OCRA community who supported your work, what would you say?

Scientists work tirelessly to turn cancer from an impossible disease to a curable and “regular” disease. This work would not be possible without the support of the OCRA community. Thank you!

See more OCRA-funded ovarian cancer immunotherapy research projects.