Marta Torroella-Kouri, Ph.D.

Research Assistant Professor of Microbiology and Immunology
Room 3031 Rosenstiel Medical Sciences Building
1600 NW 10th Avenue
Telephone: 305-243-6260
Fax: 305-243-4623

Research Interests

The progression of a cancer is generally associated with the development of an immunosuppressed condition in the host. Indeed, in the process of cancer development, the tumor exhibits diverse mechanisms that enable it to take over the host’s immune system, facilitating expansion of the malignant growth and the ultimate death of the host. The mechanisms displayed by a tumor in order to reach this state of immune unresponsiveness in the host are several and quite complex. Macrophages are important cells operating in the innate compartment of the immune system with crucial effector functions: they are cytotoxic for bacteria, viruses and tumor cells. However, there is growing evidence that, as opposed to T cells, which provide a sign of good prognosis when colonizing tumors, the presence of macrophages in tumors confers the signature of an aggressive tumor behavior, as if macrophages were cooperating with cancer progression. How a tumor manages to modulate the once responsive and protective immune system into one that is tolerant and, in some cases, even cooperative with tumor progression, constitutes the center of my current research interests. Particularly, the role of innate immunity, and especially of macrophages, in the interplay between a tumor and the host’s immune system, constitutes the focus of my current research activities.

We have shown that peritoneal elicited macrophages from mice bearing a transplantable mammary tumor are profoundly dysfunctional, exhibiting, among other things, a severely decreased production of cytokine IL-12 and of nitric oxide, two crucial proinflammatory molecules. Most interesting, we have recently demonstrated the existence of substantially diminished expression of NFkB and C/EBP in tumor bearer’s macrophages, two transcription factors centrally involved in the regulation of key proinflammatory genes. NF k B is known to display an elevated activity in tumor cells, but we have found the opposite in macrophages from tumor hosts. We believe that these findings might suggest the existence of a more general phenomenon explaining tumor-induced immunosuppression. Decreased expression of these transcription factors has also been detected in other cells of the immune system, such as Tsplenocytes from tumor bearing mice, as well as in other tumor models. There is proof that tumor-derived factors play an important role in the modulation of immune effector cells during mammary tumorigenesis. We have obtained preliminary evidence that some of the factors secreted by a tumor cell line isolated from our experimental mammary tumor might be involved in the downregulation of these transcription factors. We are currently working to identify the molecular mechanisms that might explain this phenomenon. In the near future, we plan to investigate whether this phenomenon is also extensive to tumor-associated macrophages and myeloid suppressor cells.

Previous work

Previous to our research in tumor immunology, we have worked in other cancer research fields, such as genetic toxicology and cancer molecular epidemiology. Our investigation in those fields has been focused mainly in the genetic toxicology of chemical compounds of environmental and industrial relevance; also, in the impact of oncogenes and tumor suppressor genes in the prognosis and risk assessment of breast cancer, as well as in the role of Human papillomavirus (HPV) in the etiology of cervical and oral cancer.

Selected publications:

Torroella-Kouri M, Ma X, Perry G, Ivanova M, Cejas PJ, Owen J, Iragavarapu-Charyulu, V and Lopez DM (2005), Diminished expression of transcription factors NF k B and C/EBP underlie a novel tumor evasion mechanism affecting macrophages of mammary tumor-bearing mice,
Cancer Research, 65: (22): 10578-10584.

Owen J, Lopez, D, Guthrie K, Herbert, LM, Grosso, JF, Torroella-Kouri M and Iragavarapu- Charyulu,V, (2005), The expression of CCL-2 by T lymphocytes of mammary tumor bearers: Role of tumor-derived factors, Cellular Immunology 235:122-135.

DiNapoli M, Torroella-Kouri M, Perry G and Lopez DM (2005), Diminished PKC activity and decreased binding of transcription factors are involved in the impaired production of nitric oxide by macrophages from tumor-bearing mice, Int. J. Molecular Medicine, 15(13): 503-512.

Torroella-Kouri M , Herbert LM, Perry G and Lopez DM (2004) Altered IL-12 Signaling Pathways Contribute to the Deficient IFN-gamma Production by T Splenocytes from Tumor-Bearing Mice, Cancer Genomics and Proteomics 1:345-354.

Torroella-Kouri M and DM Lopez, (2003), Mammary tumor-derived TGF-b1 impairs crucial innate immune responses in tumor hosts, J of Immunology and Immunopathology, 5 (1):31-38.

Torroella-Kouri M , J Keith, M Ivanova and D Lopez, (2003) IL-11 induced reduction of C/EBP transcription factor binding may contribute to the IL-12 downregulation in tumor-bearing mice,
Int J Oncology, 22 (2): 439-48.

Berho M, Torroella-Kouri M, Viciana A, Weppler D, Thompson J, Nery J, Tzakis A and Ruiz P (1998) Adenovirus enterocolitis in human small bowel transplant, Pediatric Transplantation, 2:277-282.

Torroella-Kouri M, Morsberger S, Carrillo A, Mohar A, Meneses A, Ibarra M, Daniel RW, Ghaffari A and Shah KV (1998), HPV prevalence among Mexican women with and without cervical neoplasia, Gynecologic Oncology,70:115-20.

Bosch FX, Manos MM, Munoz N, Sherman M, Jansen AM, Peto J, Schiffman MH, Moreno V, Kurman R, Shah KV and the International Biological Study on Cervical Cancer Study Group (where Torroella-Kouri M is included) (1995) HPV prevalence in cervical cancer: a worldwide perspective, J of the National Cancer Institute, 87 no. 11 pp.796-802.

Zelada-Hedman M, Torroella-Kouri M, Mesquita R, Nordenskjold M, Skoog L, Lindblom A, (1994) Loss of heterozygosity studies in tumors from families with breast-ovarian cancer syndrome, Human Genetics, Sep 94 (3) 231-234.

Zelada-Hedman M, Werer G, Collins P, Backdahl M, Perez I, Franco S, Jimenez J, Cruz J, Torroella-Kouri M, Nordenskjold M and Lindblom A (1994) High expression of the EGF-R in fibroadenomas compared to breast carcinomas, Anticancer Research 14:1679-88.

Peyton CL, Jansen AM, Wheeler CM, Stewrat AC, Peto J, Bosch FX, Munoz N, Teyssie AR, Torroella-Kouri M, Wabinga HR, Sarjadi, Ngelangel C and Manus MM (1994) A novel Human Papillomavirus sequence from an international cervical cancer study, J of Infectious Diseases, 170:1093-95.

Rangel LM, Ramirez M, Torroella-Kouri M, Pedroza A, Ibarra V and Gariglio P (1994) Multistep Carcinogenesis and Genital Papillomavirus infections: implications for diagnosis and vaccines, Archives of Medical Research, Mexico, vol 25 no. 2 pp. 262-72.

Ramirez M, Torroella-Kouri M and SantanaJ (1993) Human Papillomavirus DNA detection in neoplastic oral lesions as well as in normal oral tissue, Rev del Instituto Nacional deCancerologia, Mexico, vol. 39 no. 2 Abr-Jun pp. 1820-24.

Torroella-Kouri M , Skoog L, Nordenskjold M, Larsson C and Bystrom C (1991) Oncogene amplification in human breast cancer: amplification of neu oncogene in carcinomas and rearrangement of the EGF-R gene in a phyllodes sarcoma. Rev Biotecnologia Aplicada , Cuba , 8 no. 2 pp 182-90.

Books and monographs published:

Torroella-Kouri M and Villa Trevino S (1998) Genetic Basis of Cancer, book. Fondo de Cultura Economica (eds), Mexico.

Torroella-Kouri M (1994) Molecular Mechanisms in Human Carcinogenesis, booklet. Instituto Tecnologico y de Estudios Superiores de Monterrey, Mexico.