Li Lily Wang, PhD
Lerner Research Institute,
9500 Euclid Avenue, Cleveland, Ohio 44195
The current research interest of our laboratory is to define the mechanisms by which immune checkpoint proteins regulate anti-tumor immune responses and to develop rational therapeutics for cancer immunotherapy.
Specifically, we focus on delineating the mechanisms by which a novel immune checkpoint protein, V-domain Immunoglobulin Suppression of T cell Activation (VISTA), modulates immune responses to tumors. Our research group has published a series of original research and review articles that address the inhibitory roles of VISTA during the development of anti-tumor immunity, autoimmunity, and inflammatory diseases. We have shown that VISTA is a critical immune checkpoint protein that controls myeloid cell- and T cell-mediated anti-tumor immunity, therefore is a valuable target for cancer immunotherapy.
Currently, we are committed to discovering novel inhibitory receptors that interact with VISTA and developing effective approaches that block VISTA-mediated immune checkpoint pathway and improve the efficacy of cancer immunotherapy.
Figure 1. The B7 family co-signaling molecules regulate T cell responses. Co-inhibitory molecules, such as CTLA-4, PD-1, and VISTA are also called “immune-checkpoint proteins”. They play a critical role in maintaining T cell peripheral tolerance and controlling autoimmunity.
Figure 2. V-domain Immunoglobulin Suppression of T cell Activation (VISTA) is a novel immune-checkpoint protein that regulates both innate and adaptive immunity against cancer.
Figure 3. A VISTA-blocking monoclonal antibody synergizes with a cancer vaccine to eradicate tumor cells and improve host survival.
- Le Mercier I, Chen W, Lines JL, Day M, Li J, Sergent P, Noelle RJ, Wang L (2014) VISTA regulates the development of protective anti-tumor immunity. Cancer Research, 74:1933-1944. PMC4116689,
- Lines JL, Pantazi E, Mak J, Sempere LF, Wang L, O'Connell S, Ceeraz S, Suriawinata AA, Yan S, Ernstoff MS, Noelle RJ. (2014) VISTA is an immune checkpoint regulatory molecule for human T cells. Cancer Research, 74:1924-1932. PMC4085258.
- Lines JL, Sempere LF, Broughton T, Wang L, Noelle RJ. (2014) VISTA Is a Novel Broad-Spectrum Negative Checkpoint Regulator for Cancer Immunotherapy. Cancer Immunology Research, Jun;2(6):510-7. PMC4085258.
- Wang L*, Le Mercier I, Putra J, Chen W, Liu J, Schenk AD, Nowak EC, Suriawinata AA, Li J, Noelle RJ. (2014) Disruption of the immune-checkpoint VISTA gene imparts a proinflammatory phenotype with predisposition to the development of autoimmunity. Proc Natl Acad Sci U S A. (41):14846-51, PMC4205642 *Corresponding author, shared senior authorship.
- Liu J, Chen W, Putra J, Yuan Y, Suriawinata AA, Schenk AD, Miller H, Guleria I, Barth RJ, Huang YH, Wang L (2015) Immune-checkpoint proteins VISTA and PD-1 nonredundantly regulate murine T-cell responses. Proc Natl Acad Sci U S A. 112(21):6682-7. PMC4450438
- Li N, Yuan Y, Xu W, Ayithan N, Imai Y, Wu X, Miller H, Olson M, Feng YF, Huang YH, Turk MJ, Hwang ST, Malarkannan S, Wang L (2017)VISTA regulates Imiquimod-induced skin inflammation via controlling the inflammatory cytokine production and gd T cell activation. Scientific Report. 2017 May 3;7(1):1485. PMC5431161
- Xu W, Tạ MH, Malarkannan S, Wang L (2018) Review: The structure, expression, and function of immune-checkpoint protein VISTA as a critical regulator of anti-tumor immunity, autoimmunity, and inflammation. Cellular & Molecular Immunology. 2018 May 15(5):438-446 PMC6068175
- Xu W, Dong J, Zheng Y, Zhou J, Yuan Y, Ta H, Miller H, Olson M, Rajasekaran K, Ernstoff M, Wang D, Malarkannan S, Wang L (2019) Immune checkpoint protein VISTA regulates anti-tumor immunity by controlling myeloid cell-mediated inflammation and immunosuppression. Cancer Immunology Research , In press
Drs. Mian, Gupta and Hwang—a multi-disciplinary team of researchers and clinicians—will look for ways to optimize immune checkpoint inhibitor therapy, including testing novel combinatory treatments and identifying predictive biomarkers of treatment response.