Overacre-Delgoffe AE, Bumgarner HA, Cillo AR, Burr AHP, Tometich JT, Tabib T, Lafyatis R, Vignali DAA, Hand TW. “Microbiota-specific T cells drive tertiary lymphoid structures and anti-tumor immunity in colorectal cancer.” Immunity. 2021. Dec 14. doi: 10.1016/j.immuni.2021.11.003.
Overacre-Delgoffe AE, Hand, TW. “Regulation of Tissue-Resident T cells by the Microbiota.” Mucosal Immunology. 2021. Feb 22. doi: 10.1038/s41385-022-00491-1.
Overacre-Delgoffe AE, Chikina M, Dadey RE, Yano H, Brunazzi EA, Shayan G, Horne W, Moskovitz JM, Kolls JK, Sander C, Shuai Y, Normolle DP, Kirkwood JM, Ferris RL, Delgoffe GM, Bruno TB, Workman CJ, Vignali DAA. “Interferon-γ drives Treg fragility to promote anti-tumor immunity.” Cell. 2017 June 1;169(6):1130-1141. doi: 10.1016/j.cell.2017.05.005.
Previewed in Cell. Highlighted in Science Daily, Medical News Today, World Pharma News, and other news outlets. Cited >200x.
Overacre-Delgoffe AE, Vignali, DA. “Treg fragility: a prerequisite for effective anti-tumor immunity?” Cancer Immunology Research. 2018 Aug;6(8):882-887. doi: 10.1158/2326-6066.
Overacre AE, Vignali, DA. “Treg stability: to be or not to be?” Curr Opin Immunol. 2016 Jan 14;39:39-43. doi: 10/1016/j.coi.2015.12.009.
Overacre AE, Kurtulus S, Sznol M, Pardoll D, Anderson A, Vignali DA. “Combination immunotherapy: Where do we go from here?” JITC. 2015 Aug 3:38.
- MicrobiomeImmunotherapy
- Regulatory T cells
- Microbiota-specific T Cells
- Immunotherapy-refractory cancers
The Overacre Lab is interested in how the microbiota:immune system relationship impacts cancer progression and immunotherapeutic response in both local and distant tumors.
Gut microbes impacting distant tumors
The gut microbiota dramatically impacts melanoma patient response to current immunotherapies. However, how or why this occurs as well as whether this happens at other distant tumor sites is unknown. Working in both mouse and man, we hope to uncover the mechanisms by which colonic residing bacteria benefit (or inhibit) an effective anti-tumor response during immunotherapy.
Microbiota-specific T cells in cancer
We have shown that microbiota-specific CD4+ T cells are required for anti-tumor immunity in colorectal cancer after microbe modulation. Now, we hope to take things a step further and understand how the local microbiota impacts T cells from the naïve to the terminally exhausted.
Microbiota-driven immunoregulation
Regulatory T cells (Tregs) are a critical cell population to protect against and control autoimmunity and unchecked inflammation. However, they are also a major barrier to effective anti-tumor immunity and immunotherapeutic response. Microbiota-specific, peripherally induced Tregs (pTregs) are a unique population found within the gastrointestinal tract that are required for maintaining tolerance and homeostasis within the gut. We are interested in fine-tuning these cells to improve immunotherapy while limiting toxicity and irAEs.