Cancer Immunology, Inflammation & Tolerance


The principal goals of the program are to elucidate molecular pathways and cellular processes active in tumor microenvironments in order to develop, characterize, and apply immunological approaches to prevention, diagnosis, treatment, and monitoring of premalignant and malignant diseases. Specific aims include:

  • Discovery research using models of chronic inflammatory diseases (i) to elucidate how immune responses are regulated to create tolerance (unresponsiveness) in tumor microenvironments that inhibit natural and vaccine-induced anti-tumor immunity and (ii) to identify novel targets for therapeutic intervention;

  • Development and characterization of molecular and immunological strategies for manipulating innate and adaptive immune responses to malignancy;

  • Translating new discoveries into clinical settings in collaboration with experimental oncologists in the Georgia Cancer Center and corporate partners;

  • Evaluating the efficacy of immunotherapy and conventional therapies by developing a system to monitor immune response in conjunction with clinical outcomes;

  • Understanding how chronic inflammation creates tolerance to protect tumors and healthy tissues from immune-mediated injury;

  • Manipulating tolerogenic mechanisms for clinical benefit;

  • Developing better cancer vaccines;

  • Elucidating novel targets to manipulate immune responses to treat cancer and other chronic inflammatory syndromes.

Using the body's immune system: a dual approach

McGaha

Pre-malignant lesions form tumors by evading natural immunity before clinical presentation, and established tumors are resistant to tumor vaccines because immune tolerance attenuates vaccine-induced immunity. Successful therapies must therefore disrupt local microenvironments that protect tumors. Hence, program research focuses on tolerogenic pathways in the innate and adaptive immune systems that protect healthy tissues and tumors from immune-mediated destruction, and on translational opportunities to treat cancer patients arising from this research.

Researchers in the CIT program use a range of techniques to study how the immune system influences tumorigenesis and cancer therapy. The immune system can inhibit or promote tumor progression in local tissues where pre-malignancies form. Major program themes are to elucidate, (i) how pre-malignancies create and sustain local immunologic tolerance necessary for tumor formation and, (ii) how to destroy local tolerance that protects tumors from natural and vaccine-induced anti-tumor immunity. Since loss of immune tolerance leads to autoimmune syndromes (e.g. type I diabetes, systemic lupus erythematosus, rheumatoid arthritis, colitis, multiple sclerosis), program investigators use mouse models of cancer and autoimmune progression to elucidate critical molecular and cellular pathways that either create or destroy immune tolerance.

The scientific rationale for this dual approach is that pre-malignant cells create and sustain tolerance during tumor progression, while breaking tumor-associated tolerance is necessary for successful anti-tumor treatment. Hence, program goals are to elucidate molecular and cellular pathways at sites of inflammation that promote or break immune tolerance using pre-clinical mouse models of tumor progression and autoimmune syndromes, and developing novel immunotherapies to treat these syndromes more effectively by targeting tolerance pathways. To this end, program faculty also engage in promoting pre-clinical research and early-phase clinical trials of novel vaccine adjuvants to improve cancer immunotherapy, in some cases with corporate partners. To pursue these focused research themes and scientific goals, program faculty employ many state-of-the-art techniques, facilities, and unique resources, including flow cytometric sorting and analysis, a range of molecular imaging techniques, genomic analysis, and genetically modified mouse strains. Future program development will build on existing CIT program strengths
by recruiting new investigators with expertise in inflammation, immunological, and metabolic research to complement current research focused
on regulation of adaptive immunity.