Overcoming immune suppression in haematological malignancies

Despite intensification of chemotherapeutic regimens, survival rates in acute myeloid leukaemia (AML) have plateaued. Immune checkpoint inhibitors (ICIs) have been shown to be effective in many cancers, but their efficacy in AML has not been clearly established. To better understand the immune landscape of the AML microenvironment, we perform immunophenotyping on fresh bone marrow cells from AML patients. In addition, we perform assays to evaluate T-cell function and determine whether AML bone marrow T cells can be modified by ICI treatment. So far, we have confirmed that T-cell function is suppressed in the bone marrow of a subset of patients with AML. We find that in some instances this suppression can be reversed by blocking immune checkpoint pathways. We are also developing mouse models of leukaemia that recapitulate the mutational profile present in patients with AML. Our models have been genetically modified to contain both a proliferative mutation (FLT3-ITD) and a mutation that results in epigenetic dysregulation (TET2) at the level of DNA methylation. This allows us to test combination therapies based on small molecule TKIs, epigenetic modifiers and immune therapies in vivo. The ultimate goal of the Lind lab is to understand how haematological malignancies avoid immune detection and to target those pathways for clinical application.

Evan Lind is currently an Assistant Professor in the departments of Molecular Microbiology and Immunology (MMI) and Cell, developmental and Cancer Biology (CDCB) at Oregon Health and Science University (OHSU) in Portland Oregon USA. He is also a Member of the Knight Cancer Institute at OHSU. He earned his Bachelor of Arts in Biology at New York University in 1996 and his PhD in Immunology in 2007 at Dartmouth Medical School, New Hampshire USA. Dr Lind’s thesis work was performed under the mentorship of Dr Randolph Noelle and focused on biochemical pathways controlling dendritic cells ability to cross-present antigens. After completing his PhD, Dr. Lind did a post-doctoral fellowship in the laboratory of Dr. Pamela Ohashi at the Princess Margaret Hospital in Toronto, Canada.  The main focus of his research in Toronto was to understand the impact of micro-RNAs on immune function.  In his later years in Toronto, Dr. Lind collaborated with Dr. Tak Mak to develop and study novel mouse models of leukemia. In 2014 Dr. Lind was recruited to OHSU and opened his lab with a major focus on studying the immune microenvironment in leukemia in both mouse models and man.