Cancer chemotherapy offers short-term clinical benefits to many cancer patients, and yet it comes with detrimental side-effects on both primary and secondary lymphoid organs, leading to localized and systemic suppression of antitumor immunity. In-depth understanding of the mechanistic underpinnings behind chemotherapy-mediated modifications of these tumor and immune cell microenvironments will lead to promising pharmacological interventions in the course of metastatic progression. To answer this complex research question repertoire, our creative team operates in a multidisciplinary environment, in which we actively develop transgenic and xenograft mouse models of various solid carcinomas, and utilize advanced microscopy (i.e. multiplex and high-throughput immunofluorescence, multiphoton intravital imaging, and electron microscopy) and computational/digital pathology, to investigate the contextual prerequisites of chemotherapy-mediated lesions in tumor microenvironments, as will as in primary/secondary lymphoid organs, together promoting metastasis.

Key Publications:

Prometastatic and Immunosuppressive Responses of the Tumor Microenvironment to Cytotoxic Chemotherapy:

[1] Karagiannis, G.S., Bianchi, A., Sanchez, L.R., Ambadipudi, K., Cui, M.H., Anampa, J.M., Asiry, S., Wang, Y., Harney, A.S., Pastoriza, J.M., Lin, Y., Chen, X., Jones, J.G., Entenberg, D., Haddad, D., Hodges, L.J., Duong, T.Q., Sparano, J.A., Oktay, M.H., Branch, C.A., Condeelis, J.S. Assessment of MRI to Estimate Metastatic Dissemination Risk and Prometastatic Effects of Chemotherapy. NPJ Breast Cancer, 2022; 8: 101.

[2] Asiry, S., Kim, G., Filippou, P.S., Rivera Sanchez, L., Entenberg, D., Marks, D.K., Oktay, M.H., Karagiannis, G.S. The Cancer Cell Dissemination Machinery as an Immunosuppressive Niche: A New Obstacle Towards the Era of Cancer Immunotherapy. Frontiers in Immunology, 2021; 12: 654877.

[3] Karagiannis, G.S., Condeelis, J.S., Oktay, M.H. Chemotherapy-Induced Metastasis: Molecular Mechanisms, Clinical Manifestations, Therapeutic Interventions. Cancer Research, 2019; 79: 4567-4576.

[4] Karagiannis, G.S., Pastoriza, J.M., Wang, Y., Harney, A.S., Entenberg, D., Pignatelli, J., Sharma, V.P., Xue, E.A., Cheng, E., D’Alfonso, T.M., Jones, J.G., Anampa, J., Rohan, T.E., Sparano, J.A., Condeelis, J.S., Oktay, M.H. Neoadjuvant Chemotherapy Induces Breast Cancer Metastasis through a TMEM-mediated Mechanism. Science Translational Medicine, 2017; 9: eaan0026.