The long-term objective of these studies is to determine whether a unique set of CD8 T cells can play a role in cancer therapy using the immune system. Specifically, we and others found that CD8 (killer) T cells that secrete a chemical substance (cytokine) known as interleukin-17 (IL-17) appear to last longer and function better than those that secrete other cytokines. We plan to determine how these cells (called Tc17) kill tumors, and whether they absolutely need IL-17 to work. Next, we plan to figure out the best way to make these cells, focusing on whether the target they recognize (antigen) plays a major role in that process. Finally, we found that Tc17 cells show an extremely interesting property that might be important for their superior anti-tumor function: in animals these cells convert, or flip the cytokines they produce. This conversion process is fascinating, and a better understanding of it might be important in understanding how other tumor treatments that use the immune system work. These experiments will not be undertaken in a vacuum;several groups, including ours have already showed that CD8 T cells that make IL-17 have superior anti-tumor activity in animals. Thus, these studies are designed to follow up on those intriguing results in an effort to engineer and understand a superior method for cancer treatment.

Public Health Relevance

This project is directly relevant to cancer treatment, a significant public health problem. Using an animal model, we will investigate a new method for cancer treatment that uses a patient's own immune cells to attack tumors;these cells will be removed from the body, manipulated in a novel way, and then returned. If our animal studies are successful, similar methods can be readily tested in humans.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Cancer Immunopathology and Immunotherapy Study Section (CII)
Program Officer
Mccarthy, Susan A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Johns Hopkins University
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Gordy, James T; Luo, Kun; Francica, Brian et al. (2018) Anti-IL-10-mediated Enhancement of Antitumor Efficacy of a Dendritic Cell-targeting MIP3?-gp100 Vaccine in the B16F10 Mouse Melanoma Model Is Dependent on Type I Interferons. J Immunother 41:181-189
Francica, Brian J; Ghasemzadeh, Ali; Desbien, Anthony L et al. (2018) TNF? and Radioresistant Stromal Cells Are Essential for Therapeutic Efficacy of Cyclic Dinucleotide STING Agonists in Nonimmunogenic Tumors. Cancer Immunol Res 6:422-433
Andrews, Lawrence P; Marciscano, Ariel E; Drake, Charles G et al. (2017) LAG3 (CD223) as a cancer immunotherapy target. Immunol Rev 276:80-96
Topalian, Suzanne L; Drake, Charles G; Pardoll, Drew M (2015) Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell 27:450-61
Sharabi, Andrew B; Nirschl, Christopher J; Kochel, Christina M et al. (2015) Stereotactic Radiation Therapy Augments Antigen-Specific PD-1-Mediated Antitumor Immune Responses via Cross-Presentation of Tumor Antigen. Cancer Immunol Res 3:345-55