Sheila DroverAssociate Professor of Immunology M.Sc., Ph.D. Memorial
BioMedical Sciences Immunology
Faculty of Medicine Memorial University of Newfoundland Health Sciences Centre St. Johnâ€TMs, NL Canada, A1B 3V6 Office: H1846 Labs: H1835/1844-45
DESCRIPTION OF RESEARCH – IMMUNE MARKERS AND IMMUNOMODULATION IN BREAST CANCER
The Drover laboratory previously showed that patients with breast cancer had a better outcome if their tumor cells expressed certain types of HLA molecules, contained large numbers of infiltrating CD4+T-cells and expressed high levels of IFN-γ. We also found that HLA expression and evidence of immunity depended on the type of breast cancer. Cancer cells can escape immune destruction due to upregulation of inhibitory or checkpoint molecules such as PD-1 and LAG3 on immune cells and PD-L1 on cancer cells. However, these inhibitory and other molecules can be targeted by drugs such as immune checkpoint inhibitors and small kinase inhibitors. Our current work is focusing on two areas 1) investigating the mechanism of deregulated IFN-γ and HLA pathways in HER2-positive breast cancer and 2) immunomodulation of HLA and PD-L1 on cancer cell lines using small kinase inhibitors and targeted immune therapeutics.
Funding for Dr. Drovers’ research has come from various sources: Medical Research Foundation Awards at Memorial University, Canadian Breast Cancer Research Alliance, Medical Research Council, CIHR and RDC, Canadian Breast Cancer Foundation, (Atlantic Chapter).
Mostafa AA, Codner D, Hirasawa K, Komatsu Y, Young MN, Steimle V, Drover S Activation of ERα signaling differentially modulates IFN-γ induced HLA-class II expression in breast cancer cells. PLoS One. 2014 Jan 27;9(1):e87377
Robila V, Ostankovitch M, Altrich-Vanlith ML, Theos AC, Drover S, Marks MS, Restifo N, Engelhard VH.
MHC class II presentation of gp100 epitopes in melanoma cells requires the function of conventional endosomes and is influenced by melanosomes. J Immunol. 2008 Dec 1;181(11):7843-52.
Oldford SA, Robb JD, Codner D, Gadag V, Watson PH, Drover S.Tumor cell expression of HLA-DM associates with a Th1 profile and predicts improved survival in breast carcinoma patients. Int Immunol. 2006 Nov;18(11):1591-602.
Oldford SA, Robb JD, Watson PH, Drover S. HLA-DRB alleles are differentially expressed by tumor cells in breast carcinoma. Int J Cancer. 2004 Nov 10;112(3):399-406.
Campoli M, Chang CC, Oldford SA, Edgecombe AD, Drover S, Ferrone S.
HLA antigen changes in malignant tumors of mammary epithelial origin: molecular mechanisms and clinical implications. Breast Dis. 2004;20:105-25. Review.
Spurrell DR, Oldford SA, Frost T, Larsen B, Codner D, Edgecombe A, Drover S. Discordant expression of HLA class II-associated co-chaperones and HLA-DRB alleles in cultured fibroblast-like synoviocytes. Hum Immunol. 2004 Dec;65(12):1516-29.