Basic Immunological Mechanisms
All therapeutic advances in cancer immunology are based on our growing understanding of fundamental immunological mechanisms. We believe that the intricate regulation of immune responses provides many points of intervention for cancer immunotherapy. It is well-established in human cancers that the presence of particular immune cell populations — such as activated cytotoxic T cells — strongly correlates with survival.
Several labs in the Department of Cancer Immunology and Virology (CIV) study the function of T cells at a cellular and molecular level, and are identifying novel targets for enhancing T cell-mediated responses in cancer (Cantor, Glimcher, Wucherpfennig, Agudo, Dougan, Rashidian). Additionally, we study the basic biology of myeloid cells including macrophages and dendritic cells, as well as the metabolic pathways that regulate myeloid cell function (Mills, Wucherpfennig). An important area of emphasis is innate immune signaling, such as the cGAS-STING pathway, that regulates anti-viral and anti-tumor immune responses (Kranzusch). We also study intracellular regulatory pathways in immune and cancer cells, including mechanisms of protein translation (Lee).
Cancer Immunology and Immunotherapy
The CIV department develops novel approaches for immunotherapy. We also collaborate with our clinical colleagues to advance important discoveries into clinical trials. Our efforts are closely integrated with translational and clinical programs for several major cancer types, including pancreatic cancer (Dougan), ovarian cancer (Glimcher), breast cancer (Agudo and Wucherpfennig) and glioblastoma (Wucherpfennig).
Our department has deep expertise in T cell biology, and many of our efforts focus on strategies to enhance anti-tumor T cell function. The Wucherpfennig lab is emphasizing the discovery of negative regulators of T cell function, which has already led to the identification of novel therapeutic targets that are being evaluated in clinical trials. The Cantor Lab is studying CD8 regulatory T cells based on the discovery that depletion of this cell population enhances anti-tumor responses in mouse models. The Agudo lab is studying immune evasion mechanisms from T cell-mediated immunity by cancer stem cells and metastases, and has shown that quiescent cancer cells form immunosuppressive niches that inhibit cytotoxic T cells. The Glimcher lab is studying the mechanisms by which T cell and dendritic cell function is inhibited in ovarian cancer.
We also emphasize the in-depth study of the tumor microenvironment using cutting-edge spatial technologies in human cancers and animal models (Wucherpfennig, Agudo, Dougan). These spatial technologies offer unprecedented opportunities to study immune cell action directly within human cancers and to discover key determinants of effective anti-tumor immune responses. To that end, the Wucherpfennig and Agudo labs have established the Molecular Imaging Core Facility, which provides access to spatial proteomics and transcriptomics technologies for all of our investigators.
A major goal of the CIV department is to develop the next generation of cancer therapies, bridging discovery and clinical translation. We have built a major program on novel protein therapeutics (Rashidian, Marasco and Wucherpfennig), and several of these therapeutics are being evaluated in ongoing clinical trials. We are also developing protein-based imaging probes to enable early and precise detection of cancer and inflammation with non-invasive PET imaging (Rashidian). Finally, we have major ongoing efforts on the development of next generation CAR T cell therapies. These include the discovery of novel targets for CAR T cells, the development of therapeutic payloads, and the design of logic circuits for precise regulation of CAR T cell function (Rashidian, Marasco, Wu, Wucherpfennig).
Viral Immunology
HIV infects a critical population of immune cells (CD4 T cells), resulting in an immunodeficiency syndrome that predisposes to opportunistic infections and cancer. A shared interest by HIV and cancer immunology investigators is the development of vaccines that stimulate strong CD8 T cell responses. Also, there are fundamental similarities in the molecular mechanisms that impair the function of CD8 T cells in chronic HIV infection and cancer. In both settings, chronic antigen exposure results in upregulation of inhibitory receptors (such as PD-1) that impair cytotoxic T cell function (T cell exhaustion).
The study of the HIV virus has a long-standing history at Dana-Farber, and our group has made important contributions to our understanding of: the structure of key HIV proteins (Sodroski, Engelman); the mechanism of viral integration in the genome of infected CD4 T cells (Engelman); and the mechanisms by which the virus causes neuro-AIDS and establishes a reservoir in the CNS (Gabuzda). The Marasco Lab has developed phage-display-based antibody libraries that enable isolation of human antibodies against virtually any antigen. These libraries are being used for isolation of neutralizing antibodies against influenza and emerging viral pathogens.
Our Investigators
Learn more about our Cancer Immunology and Virology team members and their research.