Assistant Member
Department of Immunology
Roswell Park Cancer Institute
Elm and Carlton Streets
Buffalo, NY 14263
Tel: (716) 845-3963
Xuefang.Cao@RoswellPark.org

Dr. Xuefang Cao joined the faculty of Roswell Park Cancer Institute (RPCI) in 2008 as an Assistant Member in the Department of Immunology.

Dr. Cao earned a medical degree from Hebei Medical University in China in 1994 and a PhD degree from University of Florida in 2003, and completed his postdoctoral fellowship in Division of Oncology at Washington University in St. Louis.

Dr. Cao is a member of American Association for Cancer Research, American Society of Hematology, and American Association of Immunologists, and has authored or co-authored more than 20 journal articles and abstracts.

Research Interests
The immune system responds to tumors even though they are derived from the host. Due to genetic and epigenetic changes associated with carcinogenesis, tumor cells can express neoantigens that elicit immune responses. Immune cells infiltrate tumors and make up a significant component of the multi-cellular cancer environment, yet the immune system often fails to prevent tumor formation and progression. One explanation for this paradox is the presence of tolerance-promoting regulatory T cells (Tregs) that counteract anti-tumor immune cells. Tregs were known to be essential for maintaining peripheral tolerance (non-responsiveness) to self antigens. Recently, Tregs have been found to promote tolerance to tumors in mouse models. Moreover, Treg infiltration in human tumors and malignant ascites has been associated with worse clinical outcomes for various types of cancers. We are interested in understanding the molecular and celluar mechanims by which Tregs influence anti-tumor immune responses. Our long term goal is to develop innovative strategies that selectively break Treg-mediated tolerance to tumors, without damaging Treg-mediated self tolerance.

Our studies suggest that the lymphocyte makeup and function (Tregs vs. effector lymphocytes) in the cancer environment affect clinical outcomes. The perforin/granzyme pathway was previously known to be utilized only by effector lymphocytes (e.g. NK, CD8+ T cells) to kill host cells infected by intracellular pathogens or transformed tumor cells. Surprisingly, we have recently discovered that tumor-associated Tregs utilize granzyme B and perforin to suppress the anti-tumor activities of NK and CD8+ T cells (Immunity 2007 Oct; 27(4):635-46). Therefore, we are currently studying cancer patients and mouse models of cancer to examine the activation of this pathway in both Tregs and effector lymphocytes, and to characterize the impact on tumor initiation and progression by the activation (or deficiency) of this pathway.

Mounting evidence suggests that tumors can suppress immunity by promoting the expansion, recruitment, and activation of Tregs. We are currently developing mouse models to dissect the mechanisms of tumor-induced Treg activation and function. For example, we have found that while resting Tregs in healthy mice do not express granzyme B protein, it is highly induced in tumor-associated Tregs by local protein factors. Utilizing the mouse tumor models, we aim to identify such Treg activating factors, and to test the strategy of targeting granzyme B to break Treg-mediated tumor tolerance.