Marta Torroella-Kouri, Ph.D.
Research Assistant Professor of Microbiology & Immunology
Description of Research
Tumor cells emerge in a healthy organism and may be recognized by the immune system. This recognition generally leads to an incipient defense reaction and elimination of the original tumor cells. However, tumors do develop, which indicates that the immune system fails to completely eradicate early tumor cells. When this happens, the persistent tumor cell population may grow, resulting in a neoplasia that will progress and become malignant, i.e.: infiltrate, metastasize and kill the host. Before this occurs, a progressive decline in the immune response of the host is observed. It is known that the progression of a tumor is associated with this immune suppression, which is mainly local, in the tumor micro-environment, and in later stages of tumor progression is also systemic.
The study of the interplay between a tumor and its host, in terms of the mechanisms displayed by the tumor, that eventually control and diminish the otherwise healthy immune response of the host organism, is the center of Dr. Torroella's research. She is particularly interested in the role of the innate immune response in cancer, especially in the activity of macrophages, as targets of tumor-induced immune suppression. Tumors modulate macrophage activities and make them contribute to cancer progression, and the presence of macrophages in microenvironment is a recognized sign of poor tumor prognosis. Likewise, the tumor microenvironment modulates and modify macrophages phenotypes and functions. Dr. Torroella's laboratory works with a mouse mammary tumor model in which a profound and progressive decrease in the inflammatory function, differentiation and survival of peripheral and particularly in tumor-associated macrophages is observed in mice bearing advanced tumors. Identifying the molecular mechanisms governing macrophage functions in the context of cancer, and understanding how the host's immune response is modulated by tumor factors are important issues in designing cancer treatments.
More recently, Dr. Torroella has become interested in studying the role of tumor-promoting macrophages in the context of obesity. Obesity is a risk factor in cancer and macrophages are known to be recruited to the fat tissue, causing low-grade chronic inflammation in obese adipose tissues. Several cancers are impacted by mice and humans with breast and colon cancers. How different are tumor-associated macrophages in obese mice and humans with breast cancer? In particular in the breast, which is composed by epithelial and adipose tissues, is there a local crosstalk in the breast tumor microenvironment between adipocytes, macrophages and tumor cells that may promote higher levels of macrophage recruitment and tumor progression? Is the breast adipose tissue of obese subjects contributing to inflammation and cancer more than the breast adipose tissue from lean mice and women? Dr. Torroella is particularly attracted to studying tumor-associated macrophages in obese mice and women. African American and Latina women present with more aggressive breast cancers and also with a higher prevalence of obesity/overweight. Dr. Torroella’s laboratory is currently interested in elucidating the different characteristics of tumor-associated macrophages from obese subjects, and whether and how they may contribute to cancer progression even more than macrophages from lean individuals.
- Identified several molecular mechanisms by which macrophages residing in different locations in tumor hosts (peripheral and tumor-associated macrophages, as well as their precursor blood monocytes) are targeted by tumor factors to impair their inflammatory functions, differentiation and viability.
- Demostrated an increased gradient of macrophage impairment and a diversity in the corresponding mechanisms with the proximity to the tumor microenvironment (blood monocytes/peritoneal macrophages/ tumor-associated macrophages).
Understanding the molecular mechanisms governing macrophage functions in cancer is essential in efforts aimed at controlling and designing therapeutic strategies to treat malignant disorders. Dr. Torroella’s research is in the crossroad between tumor immunology, inflammation, and cancer and immune modulation; and has a strong basic science component as well as translational potential.
Selected Cancer-Related Publications
- Torroella-Kouri M, Silvera R, Rodriguez D, Caso R, Shatry A, Opiela S, Ilkovitch D, Schwendener RA, Iragavarapu-Charyulu V, Cardentey Y, Strbo N, Lopez DM. Identification of a subpopulation of macrophages in mammary tumor-bearing mice that are neither M1 nor M2 and are less differentiated. Cancer Res 69:4800-9, 2009. Read more »
Collaborating in the Multidisciplinary Research Program(s):