Our Science

José R. Conejo-Garcia, M.D., Ph.D.

José R. Conejo-Garcia, M.D., Ph.D.

  • Associate Professor and Program Leader, Tumor Microenvironment and Metastasis Program
  • Director of Graduate Studies
  • 215-495-6825, Office
Summary

The importance of immunosurveillance in the prevention of cancer is today beyond question among immunologists, and is further supported by the clinical success of emerging immunotherapies against otherwise drug-resistant tumors. It is now becoming increasingly clear that tumor cells express unique antigens that are recognized by the immune system. In tumors of non-viral origin, these can be newly acquired antigens resulting from mutations; differentiation antigens expressed by embryonal but not adult cells; or antigens that are co-expressed by healthy cells at low levels and do not break tolerance. The laboratory of José Conejo-Garcia is primarily focused on understanding and targeting the mechanisms that govern the balance between immunosuppression and protective immunity in the tumor microenvironment.

The framework currently accepted by most tumor immunologists (the cancer "immunoeditting" hypothesis) is that the immune system can detect the presence of nascent tumor lesions and destroy them before they become clinically obvious. These innate immune mechanisms promote the development of a tumor antigen-specific adaptive immune response that eventually relies on cytotoxic lymphocytes for tumor elimination. Even if tumors are not ultimately eliminated, they can be kept in check for long periods in a dynamic interaction with T cell subpopulations. By understanding the intrinsic and extrinsic mechanisms that restrain the activity of anti-tumor lymphocytes, Conejo-Garcia and his team are also devising strategies to create new therapies that will utilize patients’ own immune systems to elicit protective anti-tumor immunity against—and prevent recurrence of—gynecologic malignancies.

Born and educated as a physician in Spain, Conejo-Garcia’s career has evolved over the years to integrate very diverse disciplines in 4 different countries. His current research explores the biology of leukocytes of the myeloid lineage, which are co-opted by solid tumors to protect them from the immune system as a whole, rather than boosting protective immune responses. His laboratory is investigating and targeting the master regulators driving the transcriptional program behind the pathological expansion of these leukocytes in virtually all solid tumors.  Several projects in the lab investigate how to target these immune cells by either eliminating them, re-programing their immunostimulatory potential, or using them as Trojan Horses to deliver therapeutic agents to the tumor microenvironment. In complementary studies, the lab investigates new intrinsic mechanisms promoting the unresponsiveness of anti-tumor T cells, as well as the influence of the genetic background in all these processes.

Representative Publications of the Last Four Years

1.  Stephen TL, Wang H, Rutkowski MR, Allegrezza MJ, Svoronos N, Tesone AJ, Stephen TL, Perales-Puchalt A, Nguyen J, Hu H, Conejo-Garcia JR. Foxp1 mediates the immunosuppressive  effect of TGF-beta on tumor-infiltrating lymphocytes. Submitted.

2.  Rutkowski MR, Allegrezza MJ, Svoronos N, Tesone AJ, Stephen TL, Perales-Puchalt A, Nguyen J, Zhang PJ, Fiering SN, Tchou J, Conejo-Garcia JR (2013). Initiation of metastatic breast carcinoma by targeting of the ductal epithelium with Adenovirus-Cre: A novel transgenic mouse model of breast cancer. J. Vis. Exp.; In Press.

3.  Baird JR, Fox, BA, Sanders KL, Lizotte PH, Cubillos-Ruiz JR, Scarlett UK, Rutkowski MR, Conejo-Garcia JR, Fiering S, Bzik DJ (2013). Avirulent Toxoplasma gondii generates therapeutic antitumor immunity by immune activation of the immunosuppressive ovarian cancer microenvironment. Cancer Research, 73: 3842-51.

4.  Toraya-Brown S, Sheen MR, Baird JR, Barry S, Turk MJ, Hoopes PJ, Conejo-Garcia JR, Fiering S. (2012) Immune cell-mediated targeting of iron oxide nanoparticles for cancer therapy. Integr. Biol., 5: 159-71.

5.  Wasiuk A, Dalton DK, Schpero WL, Stan RV, Conejo-Garcia JR, Noelle RJ (2012). Mast cells impair the development of protective anti-tumor immunity. Cancer Immunol Immunother. 61: 2273-2282.

6.  Cubillos-Ruiz JR, Baird J, Rutkowski M, Scarlett UK,  Camposeco-Jacobs AL, Anadon-Arnillas J, Harwood N, Korc M, Fiering S, Sempere L, Conejo-Garcia JR (2012). Reprogramming tumor-associated dendritic cells in vivo using microRNA mimetics triggers protective immunity against ovarian cancer. Cancer Res., 72: 1683-1693.

7.  Scarlett UK, Rutkowski MR, Rauwerdink AM, Fields J, Escovar-Fadul X, Baird J, Cubillos-Ruiz JR, Jacobs AC, Gonzalez J, Weaver J, Fiering S, Conejo-Garcia JR (2012). Ovarian cancer progression is controlled by phenotypic changes in dendritic cells. J. Exp. Med., 209: 495-506.

8.  Robinson R.T., Khader S.A., Martino C.A., Fountain J.J., Teixeira-Coelho M., Pearl J.E., Smiley S.T., Winslow G.M., Woodland D., Walter M.J., Conejo-Garcia J.R., Gubler U. & Cooper A.M (2010). Mycobacterium tuberculosis infection induces IL12Rb1 splicing 1 to generate a novel IL12Rβ1 isoform that enhances DC migration. J. Exp. Med., 207:591-605.

9.  Nesbeth Y, Martinez D, Toraya S, Scarlett U,  Cubillos-Ruiz J,  Rutkowski M, Conejo-Garcia J. (2010) CD4+ T cells elicit host immune responses to MHC-II- ovarian cancer through CD40-mediated licensing of dendritic cells and CCL5 secretion. J. Immunol., 184: 5654-62.