Tumor Microenvironment

Tumors require complex interactions with surrounding blood vessels, immune cells, supportive tissue structures and cell types that are distinct to the tumor site in order to grow, become invasive and metastasize. Tumors influence their microenvironment by releasing soluble signals that lead to degradation and remodeling of the tissue structures that constrain their growth. Targeting the interactions of tumors with the microenvironment is an important and developing area of study.

The laboratory of Baoan Ji, M.D., Ph.D., studies how the inflammatory and fibrotic microenvironments promote the development of liver and pancreatic cancers. Dr. Ji's team developed experimental systems that specifically target oncogenes and tumor suppressors in the cells of interest. These systems can be used to temporally manipulate different genes in the same cell for therapeutic target validation and study cell-cell interactions by targeting different cell populations in the same organism.

The laboratory of Hugo Guerrero Cazares, M.D., Ph.D., focuses on the interaction of brain tumor cells with the microenvironment. Dr. Guerrero Cazares' research team is developing tools to perform cell-specific transcriptome and proteome using sophisticated and physiologically relevant brain tumor models.

Debabrata (Dev) Mukhopadhyay, Ph.D., and his team use disease models of different cancer types, including pancreatic, renal, brain and lung cancers, to examine how tumors develop and spread in the influence of the tumor microenvironment and macroenvironment. Based on that understanding, the team is working to develop potential therapeutic interventions. In addition, Dr. Mukhopadhyay's team is investigating new targeted therapy and precision vaccination strategies to substantially improve treatment for patients whose cancer is resistant to drug, radiation and immune therapies.

The laboratory of Nicole R. Murray, Ph.D., investigates the role of key proteins expressed in pancreatic cancers that can be targeted therapeutically. This group has shown that expression of the oncogene protein kinase C iota is necessary for the development of pancreatic cancer, and that excess expression suppresses anti-tumor responses from immune cells and the microenvironment. Dr. Murray's team is continuing to investigate the role of this protein in pancreatic tumor development and interaction with the host immune system.

The research goal of Tushar C. Patel, M.B., Ch.B., is to understand the mechanisms and molecules by which tumor cells communicate with other cells in liver cancers. Dr. Patel's team hopes to identify more-effective ways of treating these cancers and new tests for earlier diagnosis.

Aneel Paulus, M.D., M.S., and his research team are focused on understanding the role that various kinds of T cells play in restraining malignant B cells and plasma cells in chronic lymphocytic leukemia (CLL), Waldenstrom macroglobulinemia and multiple myeloma. Dr. Paulus' team has an extensive repository of patient bone marrow aspirate and peripheral blood biospecimens to test new treatments that are better able to restore and reengage the adaptive immune system and certain T cells to better eradicate tumor cells. Through the use of these biospecimens, early access to novel immunotherapeutics and dedicated clinical research staff, his research team has rapidly translated promising laboratory findings into early-stage clinical testing.

The research team of Derek C. Radisky, Ph.D., is defining how breast and lung cancer cells co-opt the surrounding cells and tissue structures to allow progression to invasive and metastatic stages. Through the use of sophisticated, physiologically relevant model systems, his research group defines how to target these interactions to dismantle the tumor microenvironment, to more effectively utilize existing therapies, and to develop novel and improved therapeutic strategies.

Evette S. Radisky, Ph.D., and her research team study how the activities of proteases and protease inhibitors in the tumor microenvironment can drive tumor progression. Several of these proteases are well-validated drug targets, and yet treatments targeting these proteases have been hampered by a lack of drugs with sufficient selectivity. Dr. Radisky's research team is working to develop new, more-selective drugs based on the tissue inhibitors of metalloproteinases (TIMPs), natural human proteins that in regular tissues work to regulate protease activity. Specific projects in Dr. Radisky's laboratory focus on understanding the tumor microenvironment factors that promote metastasis in highly aggressive subtypes of breast cancer and ovarian cancer.

Mark E. Sherman, M.D., studies the immune microenvironment of postpartum involution of the breast. His work aims to define mechanisms and markers that link inflammation associated with weaning to breast cancers occurring in the postpartum period using high-plex spatial analysis of protein expression and analysis of RNA and oxylipin levels. Dr. Sherman also defines immune responses in high-grade serous tubo-ovarian cancers to define heterogeneity by organ and tissue site and race in relation to clinical outcomes.

The pancreatic cancer microenvironment acts as a barrier against immune cell infiltration and chemotherapy and also provides stimuli for tumor growth. The research efforts of Peter Storz, Ph.D., determine the composition of the microenvironment that surrounds pancreatic cancer lesions, define the cell types that organize its assembly, and identify methods to modulate its composition in ways to improve therapeutic response.

The microenvironment of glioblastoma is multifaceted and consists of soluble factors, extracellular matrix components, tissue-resident cells (such as neurons, astrocytes, endothelial cells and pericytes), and immune cells that are either resident (microglia) or recruited (bone marrow-derived macrophages). The research of Nhan L. Tran, Ph.D., identifies the unique cellular composition within glioblastoma and deciphers the multifaceted bidirectional signaling network between tumor cells and the tumor microenvironment in glioblastoma tissue states to identify novel therapeutic strategies.

The laboratory of E. Aubrey Thompson, Ph.D., studies the relationship between therapeutic response in breast cancer and the tumor cell-immune cell interaction, working mainly with clinical trials and patient samples. A major effort of Dr. Thompson's research group is to develop novel technologies that facilitate analysis of the number, types, activities and locations of immune cells within high-risk breast tumors.

Daniel M. Trifiletti, M.D., investigates the impact of irradiation on the immune system, particularly in brain tumors. His team has developed novel techniques to use radiation therapy to promote the immune system to fight cancer. By sequencing novel radiation therapy with modern immunotherapies, his work is simultaneously improving cure rates and reducing side effects from treatment.