Kristin Anderson
Primary Appointment
Assistant Professor, Microbiology, Immunology, and Cancer Biology
Education
- BS, Biochemistry, University of St. Thomas
- PhD, Immunology, University of Minnesota
Research Disciplines
Cancer Biology, Immunology, Microbiology
Research Interests
Engineering cancer-killing T cells to overcome obstacles in solid tumors
Research Description
Engineering T cells to overcome suppressive signals in the tumor microenvironment
Engineered T cell therapy can effectively kill ovarian cancer cells, but there are still tumor-driven hurdles that T cells must overcome to truly beat ovarian cancer. The goals of the proposed research are to understand precisely how these tumors can block killing by T cells and to develop rational strategies to enhance cancer-killing without causing adverse side effects. Many solid tumors escape T cell therapy using the same obstacles that ovarian cancer employs, so our findings will likely help improve immunotherapies against multiple cancer types.
Engineering T cells to overcome metabolic insufficiency in the tumor microenvironment
A major limitation of adoptive T cell therapy is the progressive loss of cytotoxic T cell efficacy and survival in the tumor. One contributor to reduced efficacy is insufficient metabolic support for T cells in the tumor microenvironment. Many solid tumors have poor vascularization; combined with the increased metabolic demands of tumor cells, this can lead to local nutrient depletion and hypoxia. Notably, limitation of carbon substrates or oxygen can have profound effects on T cell behavior. Since intratumoral T cells are metabolically active and exist in a nutrient-depleted milieu, we posit that T cells may be constrained by this nutrient limitation. We hypothesize that modulating metabolic pathways active in T cells will increase the anti-tumor efficacy of engineered T cells.
Novel pre-clinical models for ovarian cancer research
Dr. Anderson previously collaborated with Dr. Venu Pillarisetty and Dr. Elizabeth Swisher to establish an organotypic slice culture system for ovarian cancer that preserves the viability, morphology and immunosuppressive features of the tumor microenvironment for approximately one week. This cutting-edge pre-clinical model provides a valuable opportunity to evaluate the potential efficacy of new therapies in a heterogeneous immune-competent setting, prior to clinical translation. The slice culture system is an improvement over standard cytotoxicity assays, which utilize two-dimensional monolayers of commercially available or primary tumor cell lines that lack many immunosuppressive structures, proteins, and cytokines in the heterogeneous tumor microenvironment. Collaborative projects aim to evaluate cutting-edge therapeutics and combination therapies, including novel immunotherapies, in this robust pre-clinical model.
Personal Statement
Selected Publications
2023
Alvarez-Breckenridge, C., Anderson, K. G., Correia, A. L., Demehri, S., Dinh, H. Q., Dixon, K. O., . . . Williams, M. M. (2023). Lessons for the Next Generation of Scientists from the Second Annual Arthur and Sandra Irving Cancer Immunology Symposium. CANCER IMMUNOLOGY RESEARCH, 11(12), 1571-1577. doi:10.1158/2326-6066.CIR-23-0522
Anderson, K. G., Braun, D. A., Buque, A., Gitto, S. B., Guerriero, J. L., Horton, B., . . . Zhang, F. (2023). Leveraging immune resistance archetypes in solid cancer to inform next-generation anticancer therapies. JOURNAL FOR IMMUNOTHERAPY OF CANCER, 11(6). doi:10.1136/jitc-2022-006533
2022
Anderson, K. G., Oda, S. K., Bates, B. M., Burnett, M. G., Suarez, M. R., Ruskin, S. L., & Greenberg, P. D. (2022). Engineering adoptive T cell therapy to co-opt Fas ligand-mediated death signaling in ovarian cancer enhances therapeutic efficacy. JOURNAL FOR IMMUNOTHERAPY OF CANCER, 10(3). doi:10.1136/jitc-2021-003959
Su, Y., Yuan, D., Chen, D. G., Ng, R. H., Wang, K., Choi, J., . . . Heath, J. R. (2022). Multiple early factors anticipate post-acute COVID-19 sequelae. CELL, 185(5), 881-+. doi:10.1016/j.cell.2022.01.014
2021
Marron, T. U., Ryan, A. E., Reddy, S. M., Kaczanowska, S., Younis, R. H., Thakkar, D., . . . Guerriero, J. L. (2021). Considerations for treatment duration in responders to immune checkpoint inhibitors. JOURNAL FOR IMMUNOTHERAPY OF CANCER, 9(3). doi:10.1136/jitc-2020-001901
2020
Morse, C. B., Voillet, V., Bates, B. M., Chiu, E. Y., Garcia, N. M., Gottardo, R., . . . Anderson, K. G. (2021). Development of a clinically relevant ovarian cancer model incorporating surgical cytoreduction to evaluate treatment of micro-metastatic disease. GYNECOLOGIC ONCOLOGY, 160(2), 427-437. doi:10.1016/j.ygyno.2020.11.009
Oda, S. K., Anderson, K. G., Ravikumar, P., Bonson, P., Garcia, N. M., Jenkins, C. M., . . . Greenberg, P. D. (2020). A Fas-4-1BB fusion protein converts a death to a pro-survival signal and enhances T cell therapy. JOURNAL OF EXPERIMENTAL MEDICINE, 217(12). doi:10.1084/jem.20191166
Manzo, T., Prentice, B. M., Anderson, K. G., Raman, A., Schalck, A., Codreanu, G. S., . . . Nezi, L. (2020). Accumulation of long-chain fatty acids in the tumor microenvironment drives dysfunction in intrapancreatic CD8+ T cells. JOURNAL OF EXPERIMENTAL MEDICINE, 217(8). doi:10.1084/jem.20191920
2019
Anderson, K. G., Voillet, V., Bates, B. M., Chiu, E. Y., Burnett, M. G., Garcia, N. M., . . . Greenberg, P. D. (2019). Engineered Adoptive T-cell Therapy Prolongs Survival in a Preclinical Model of Advanced-Stage Ovarian Cancer. CANCER IMMUNOLOGY RESEARCH, 7(9), 1412-1425. doi:10.1158/2326-6066.CIR-19-0258
2017
Anderson, K. G., Stromnes, I. M., & Greenberg, P. D. (2017). Obstacles Posed by the Tumor Microenvironment to T cell Activity: A Case for Synergistic Therapies. CANCER CELL, 31(3), 311-325. doi:10.1016/j.ccell.2017.02.008
2016
Thompson, E. A., Beura, L. K., Nelson, C. E., Anderson, K. G., & Vezys, V. (2016). Shortened Intervals during Heterologous Boosting Preserve Memory CD8 T Cell Function but Compromise Longevity. JOURNAL OF IMMUNOLOGY, 196(7), 3054-3063. doi:10.4049/jimmunol.1501797
2014
Beura, L. K., Anderson, K. G., Schenkel, J. M., Locquiao, J. J., Fraser, K. A., Vezys, V., . . . Masopust, D. (2015). Lymphocytic choriomeningitis virus persistence promotes effector-like memory differentiation and enhances mucosal T cell distribution. JOURNAL OF LEUKOCYTE BIOLOGY, 97(2), 217-225. doi:10.1189/jlb.1HI0314-154R
James, B. R., Anderson, K. G., Brincks, E. L., Kucaba, T. A., Norian, L. A., Masopust, D., & Griffith, T. S. (2014). CpG-mediated modulation of MDSC contributes to the efficacy of Ad5-TRAIL therapy against renal cell carcinoma. CANCER IMMUNOLOGY IMMUNOTHERAPY, 63(11), 1213-1227. doi:10.1007/s00262-014-1598-8
Anderson, K. G., & Masopust, D. (2014). Editorial: Pulmonary resident memory CD8 T cells: here today, gone tomorrow. JOURNAL OF LEUKOCYTE BIOLOGY, 95(2), 199-201. doi:10.1189/jlb.0913493
Anderson, K. G., Mayer-Barber, K., Sung, H., Beura, L., James, B. R., Taylor, J. J., . . . Masopust, D. (2014). Intravascular staining for discrimination of vascular and tissue leukocytes. NATURE PROTOCOLS, 9(1), 209-222. doi:10.1038/nprot.2014.005
2013
Skon, C. N., Lee, J. -Y., Anderson, K. G., Masopust, D., Hogquist, K. A., & Jameson, S. C. (2013). Transcriptional downregulation of S1pr1 is required for the establishment of resident memory CD8+ T cells. NATURE IMMUNOLOGY, 14(12), 1285-+. doi:10.1038/ni.2745
2012
Anderson, K. G., Sung, H., Skon, C. N., Lefrancois, L., Deisinger, A., Vezys, V., & Masopust, D. (2012). Cutting Edge: Intravascular Staining Redefines Lung CD8 T Cell Responses. JOURNAL OF IMMUNOLOGY, 189(6), 2702-2706. doi:10.4049/jimmunol.1201682