2024 Early Career Investigator Grant Recipient — Nicole Marjon, MD, PhD

Nicole Marjon, MD, PhD

University of Colorado - Denver

Reprograming the Ovarian Cancer Immune Microenvironment Via Inhibition of MDSC Recruitment

Project Summary

In ovarian cancer, the tumor microenvironment contributes significantly to treatment response and resistance. Targeting the immune system has been extremely successful in some tumor types, but the current immunotherapies, which primarily target T cells, have been ineffective in ovarian cancer.

T cells can be cytotoxic to cancer cells and develop memory to prevent cancer from recurring. However, the tumor microenvironment is often immunosuppressive, especially in ovarian cancer, which prevents an immune response to the cancer cells, including the T cell actions described above. One type of immune cell, myeloid derived suppressor cells (MDSCs), are extrememly immunosuppressive and tumor promoting. They are recruited to the tumor through the receptor CXCR2. We have preliminary data in a mouse model of ovarian cancer that shows decreased tumor growth after treatment with a CXCR2 inhibitor (CXCR2i). Our hypothesis is that inhibiting MDSC recruitment to ovarian tumors with a CXCR2i will allow activation of T cells, which will have an anti-tumor effect. This will be addressed in 3 aims.
Aim1: Mice with ovarian cancer will be treated with cisplatin (cis), CXCR2i, or cis+CXCR2i and evaluated for tumor growth and changes in immune cells in the microenvironment.
Aim2: Mice with ovarian cancer will be treated as in aim1 and evaluated for long-term survival as well as T cell memory.
Aim3: MDSCs will be evaluated in human tumors and correlated with clinical parameters of survival.

Bio

I am a physician scientist dedicated to improving treatments for my patients through both my clinical and research efforts. My research is focused on understanding the immune microenvironment of high grade serous carcinoma (HGSC) and developing immune targeted treatment strategies to attain durable responses for patients. Currently I am evaluating the role of myeloid derived suppressor cells in the progression of HGSC and inhibiting their migration to the tumor. My overarching goal is to cure HGSC and in the absence of that find tolerable treatments that allow for long term responses.