HANKS LAB
Tumor Immunology and Immunotherapy
Image Credit: Alpine BioVentures
Image Credit: Alpine BioVentures
Mission
We are interested in understanding the mechanisms that cancers have evolved to suppress the generation of tumor antigen-specific immune responses and how this knowledge can be exploited for the development of novel and more effective cancer immunotherapy strategies. This work involves the utilization of both autochthonous transgenic tumor model systems as well as clinical specimens to develop novel strategies to enhance the efficacy of checkpoint inhibitor and vaccine-based immunotherapies while also developing predictive biomarkers to better guide the management of cancer patients with these immunotherapy agents. While our work is focused on understanding the fundamental biochemical and metabolic pathways within the tumor microenvironment that are critical for driving immune evasion and resistance to our currently available immunotherapies, we constantly strive to translate these concepts into early phase clinical trial testing.
Research
Our work utilizes a variety of techniques and methodologies than span the breadth of basic biological research including qrt-PCR, RNAseq, multi-parameter flow symmetry, a variety of in-cell reporter assays, tandem mass spectrometry secretome analysis, as well as a variety of computational approaches to investigate murine and human genetic databases. Our work also includes a substantial effort in 1) transgenic mouse tumor studies that utilizes bioluminescence imaging with plans to move into micro-CT imaging and 2) patient-derived circulating tumor cell single cell qrt-PCR studies to assess tumor-dependent genetic alterations that occur in patients undergoing active immunotherapy.
Our current projects include:
“Lab studies show promise for a clinical trial aimed at improving current immune therapies"
“Death is no longer a foregone conclusion of stage 4 melanoma. We’re extending survival and turning melanoma into more of a chronic disease."
Lab Updates
The Hanks Lab receives funding from the Emerson Collective Foundation for developing a novel strategy to metabolically reprogram the tumor microenvironment to enhance the efficacy of checkpoint inhibitor immunotherapy.
This is a 2 year funding program targeting high-risk, high-reward projects in the biomedical sciences.
The Hanks Lab receives funding from the Duke Physician Scientist Strong Start Program to support their ongoing efforts in investigating mechanisms of immunotherapy resistance and immunotherapy toxicity in cancer.
This is 3 years of renewable funding support to further help develop a Duke research program in cancer immunotherapy.
Michael P. just completed his Ph.D. at Northwestern University where he conducted high impact studies on the role of tumor-derived exosomes and lipoprotein nanoparticles in tumor immunology. Michael P. will continue and expand our ongoing work on the role of exosomes on the modulation of the tumor immune microenvironment in both melanoma and non-small cell lung cancer.
Michael S. graduated from UNC Greensboro with a BS in Biology and gained experience in pre-clinical and clinical immuno-oncology studies before joining the Hanks Lab. We are excited to have him as part of the team!
The Hanks Lab receives funding from D3 A*STAR and Tempest Therapeutics to further studies of the roles of the Wnt signaling pathway and dendritic cell metabolism in regulating tumor-mediated immune evasion.
Michelle is currently an undergraduate at Duke University majoring in Biomedical Engineering. Michelle joins as a laboratory technician both supporting the lab as well as working on her own independent project in tumor immunology.
The Hanks Lab receives a 3 year pre-clinical research grant from Merck to investigate mechanisms of adaptive resistance to anti-PD-1 antibody immunotherapy.
Dr. DeVito was recently awarded the 2018 Damon Runyon Physician Scientist Training Award for his work exploring the role of EMT in dendritic cell tolerization and cancer immune evasion. This will be a 4 year award allowing him to establish his research efforts in the field of tumor immunology and extend the translational efforts of the lab into immuno-oncology.
Publications
Stromal Fibroblasts Mediate Anti-PD-1 Antibody Resistance via MMP-9 and Dictate TGF-β Inhibitor Therapy Sequencing in Melanoma.
Zhao, F., Xiao, C., Evans, K., DeVito, N., Theivanthiran, B., Holtzhausen, A., Siska, P.J., Blobe, G.C., and Hanks, B.A.
(2018) Cancer Immunology Research. 6(12): 1459-1471. Sept doi: 10.1158/2326-6066.CIR-18-0086. [Epub ahead of print] PMID: 30209062. In Press.
Paracrine Wnt5a-β-catenin Signaling Triggers a Metabolic Switch that Drives Dendritic Cell Tolerization and Indoleamine 2,3-dioxygenase Enzymatic Activity in the Melanoma Microenvironment.
Zhao, F., Xiao, C., Evans, K., Theivanthiran, T., DeVito, N., Holtzhausen, A., Liu, J., Liu, X., Boczkowski, D., Nair, S., Locasale, J.W., and Hanks, B.A.
(2018) Immunity. 48(1): 147-160. PMID: 29343435.
Identifying baseline immune-related biomarkers to predict clinical outcome of immunotherapy.
Gnjatic, S., Bronte, V., Brunet, L.R.; Butler, M.O., Disis, M., Galon, J., Hakansson, L.G., Hanks, B.A., Karanikas, V., Khleif, S., Kirkwood, J.M., Miller, L.D., Schendel, D.J., Tanneau, I., Wigginton, J.M., and Butterfield, L.
(2017) J ImmunoTherapy of Cancer. 5:44 PMID: 28515944
Genetic Risk Analysis of a Patient with Fulminant Autoimmune Type I Diabetes Mellitus Secondary to Combination Ipilimumab/Nivolumab Immunotherapy.
Lowe, J.R., Perry, D.J., Salama, A.K., Mathews, C.E., Moss, L.G. and Hanks, B.A.
(2016) J ImmunoTherapy of Cancer. 4:89. PMID: 28031819.
Safety and Efficacy of Radiation Therapy in Advanced Melanoma Patients Treated with Ipilimumab.
Qin, R., Olson, A., Singh, B., Thomas, S., Wolf, S., Bhavsar, N.A., Hanks, B.A., Salama, J.K., Salama, A.K.
(2016) Int J Radiat Oncol Biol Phys. 96(1): 72-77. PMID: 27375168.
Immune Evasion Pathways and the Design of Dendritic Cell-based Cancer Vaccines.
Hanks B.A.
(2016) Discov Med. 21(114):135-142. PMID: 27011049.
Melanoma-derived Wnt5a Promotes Local Dendritic-Cell Expression of IDO and Immunotolerance: Opportunities for Pharmacologic Enhancement of Immunotherapy.
Holtzhausen A., Zhao F., Evans K., Tsutsui M., Orabona C., Tyler D.S. and Hanks B.A.
(2015) Cancer Immunol. Res. 3(9):1082-95. doi: 10.1158/2326-6066.CIR-14-0167. Epub 2015 Jun 3. PMID: 26041736.
Rapid complete response of metastatic melanoma in a patient undergoing ipilimumab immunotherapy in the setting of active ulcerative colitis.
Bostwick A., Salama A. and Hanks B.A.
(2015) J Immunother Cancer 3:19. doi: 10.1186/s40425-015-0064-2. eCollection 2015. PMID: 25992290.
Early Carcinogenesis Involves the Establishment of Immune Privilege via Intrinsic and Extrinsic Regulation of Indoleamine 2,3-dioxygenase-1: Translational Implications in Cancer Immunotherapy.
Holtzhausen A., Zhao F., Evans K.S. and Hanks B.A.
(2014) Front Immunol. 5:438. doi: 10.3389/fimmu.2014.00438. eCollection 2014. PMID: 25339948.
Immunotherapy following regional chemotherapy treatment of advanced extremity melanoma.
Jiang B.S., Beasley G.M., Speicher P.J., Mosca P.J., Morse M.A., Hanks B.A., Salama A. and Tyler D.S.
(2014) Ann Surg Oncol. doi: 10.1245/s10434-014-3671-0. Epub 2014 Apr 4. PMID: 24700302.
Type III TGF-β receptor downregulation generates an immunotolerant tumor microenvironment.
Hanks B.A., Holtzhausen A., Evans K., Jamieson R., Gimpel P., Campbell O.M., Hector-Greene M., Sun L., Tewari A., George A., Starr M., Nixon, Augustine C., Beasley G., Tyler D.S., Osada T., Morse M.A., Ling L., Lyerly H.K., and Blobe G.C.
(2013) J Clin Invest. doi:10.1172/JCI65745. Epub 2013 Aug 8. PMID: 23925295.
Improved time to progression for transarterial chemoembolization compared with transarterial embolization for patients with unresectable hepatocellular carcinoma.
Morse M.A., Hanks B.A., Suhocki P., Doan P.L., Liu E.A., Frost P., Bernard S.A., Tsai A., Moore D.T., O’Neil B.H.
(2012) Clin Colorectal Cancer. 11(3):185-90. doi: 10.1016/j.clcc.2011.11.003. Epub 2012 Jan 26. PMID: 22280845.
Pharmacological inhibition of TGFβ as a strategy to augment the antitumor immune response.
Hanks B.A., Morse M.A.
(2010) Curr Opin Investig Drugs. 11(12):1342-53. PMID: 21154116.
Enhanced activation of human dendritic cells by inducible CD40 and Toll-like receptor-4 ligation.
Lapteva N., Seethammagari M.R., Hanks B.A., Jiang J., Levitt J.M., Slawin K.M., Spencer D.M.
(2007) Cancer Res. 67(21):10528-37. PMID: 17974997.
Re-engineered CD40 receptor enables potent pharmacological activation of dendritic-cell cancer vaccines in vivo.
Hanks B.A., Jiang J., Singh R.A., Song W., Barry M., Huls M.H., Slawin K.M., Spencer D.M.
(2005) Nat Med. 11(2):130-7. Epub 2005 Jan 23. PMID: 15665830.
Template-based docking of a prolactin receptor proline-rich motif octapeptide to FKBP12: implications for cytokine receptor signaling.
Soman K.V., Hanks B.A., Tien H., Chari M.V., O’Neal K.D., Morrisett J.D.
(1997) Protein Sci. 6(5):999-1008. PMID: 9144770.
Comparison of the functional differences for the homologous residues within the carboxy phosphate and carbamate domains of carbamoyl phosphate synthetase.
Javid-Majd F., Stapleton M.A., Harmon M.F., Hanks B.A., Mullins L.S., Raushel F.M.
(1996) Biochemistry. 35(45):14362-9. PMID: 8916923.
Role of conserved residues within the carboxy phosphate domain of carbamoyl phosphate synthetase.
Stapleton M.A., Javid-Majd F., Harmon M.F., Hanks B.A., Grahmann J.L., Mullins L.S., Raushel F.M.
(1996) Biochemistry. 35(45):14352-61. PMID: 8916922.
Meeting Abstracts and Presentations
Tumor-mediated Modulation of Immunometabolism as a Mechanism of Immunotherapy Resistance.
Hanks, B.
(2017) Immuno-Oncology Summit. Boston, MA. August 27, 2018
Investigating the Role of Innate Immunity in Adaptive Resistance to Cancer Immunotherapy.
Hanks, B.
(2017) Biomarkers and Immuno-Oncology World Congress. Boston, MA. June 13, 2018
A HSP-TLR-Wnt5a Paracrine Signaling Axis Drives CXCR2 Ligand Recruitment of Myeloid-derived Suppressor Cells and Represents a Novel Adaptive Resistance Mechanism to Anti-PD-1 Antibody Therapy.
Theivanthiran, B., DeVito, N., Evans, K., Zhao, F., Xiao, C., Goldschmidt, B., Edgar, R., Holtzhausen, A., Salama, A., Lewicki, J., Strickler, J., Viator, J., and Hanks, B.
(2017) Journal for Immunotherapy of Cancer. 5(Suppl 2): P385. In Press. Poster Presentation. Washington, DC.
Paracrine Wnt-β-catenin Signaling Inhibition as a Strategy to Enhance the Efficacy of Anti-PD-1 Antibody (Ab) Therapy in a Transgenic Model of Melanoma.
DeVito, N., Xiao, C., Zhao, F., Evans, K., Theivanthiran, T., Lewicki, J., Hoey, T., Hurwitz, H., Strickler, J., and Hanks, B.
(2017) Journal of Clinical Oncology. 35: (suppl; abstract 3053). Poster Presentation. Chicago, IL.
Utilizing Pre-Clinical Melanoma Models to Design Rational Combinatorial Immunotherapy Regimens
Lessons Learned from Targeting the TGF-β Signaling Pathway.
Hanks, B.A.
(2017) Melanoma Research Alliance Annual Meeting. Oral Presentation. Washington, DC.
How to Integrate Immunotherapy into Your Clinical Practice. The Immune System and Cancer: Mechanisms of Immune Suppression.
Hanks, B.A.
(2017) ASCO-SITC Joint Conference. Oral Presentation. Chicago, IL.
Paracrine Wnt5a-β-catenin Signaling Triggers a Metabolic Switch that Drives Dendritic Cell Tolerization and Indoleamine 2,3-dioxygenase Enzymatic Activity in the Melanoma Microenvironment.
Zhao, F., Xiao, C., Evans, K., Holtzhausen, A., Boczkowski, D., Nair, S., and Hanks, B.
(2016) Journal for ImmunoTherapy of Cancer. 4(Suppl 1): O11. Oral Presentation. Washington, DC.
Increased immune responses in melanoma patients pre-treated with CDX-301, a recombinant human Flt3 ligand, prior to vaccination with CDX-1401, a dendritic cell targeting NY-ESO-1 vaccine, in a phase II study.
Bhardwaj, N., Friedlander, P., Pavlick, A., Ernstoff, M., Gastman, B., Hanks, B.A., Albertini, M., Luke, J., Keler, T., Davis, T., Vitale, L.A., Sharon, S., Danaher, P., Morishima, C., Cheever, M., and Fling, S.
(2016) Journal for ImmunoTherapy of Cancer. 4(Suppl 1):P166. Poster Presentation. Washington, DC.
Stromal fibroblasts promote Wnt5a expression and suppress responses to anti-PD-1 antibody therapy in an autochthonous melanoma model.
Zhao, F., Evans, K., Xiao, C., Holtzhausen, A., and Hanks, B.A.
(2016) Journal for ImmunoTherapy of Cancer. 4(Suppl 1):P383. Poster Presentation. Washington, DC.
A Phase II Randomized Study of CDX-1401, a Dendritic Cell Targeting NY-ESO-1 Vaccine, in Patients with Malignant Melanoma Pre-Treated with Recombinant CDX-301, a Recombinant Human Flt3 Ligand.
Bhardwaj, N., Pavlick, A., Ernstoff, M., Curti, B., Hanks, B., Albertini, M., Luke, J., Yellin, M., Keler, T., Davis, T., Vitale, L., Crocker, A., Friedlander, P., Morishima, C., Cheever, M., and Fling, S.
(2016) Journal of Clinical Oncology. 34: (suppl; abstr 9589). Poster Presentation. Chicago, IL.
Tumor-mediated Metabolic Re-Programing of Dendritic Cells as a Fundamental Mechanism of Immune Tolerance and Immunotherapy Resistance.
Zhao, F., Evans, K., Xiao, C. and Hanks, B.A.
(2016) Keystone Symposium: Immunometabolism. Banff, Alberta, Canada.
Targeting the Wnt5a-β-catenin pathway in the melanoma microenvironment to augment checkpoint inhibitor immunotherapy.
Zhao, F., Evans, K., Holtzhausen, A. Tsutsui, M. Tyler, D.S., and Hanks, B.A.
(2015) Journal of Clinical Oncology. 33 (suppl; abstr 3054).
Melanoma-derived Wnt5a conditions dendritic cells to promote regulatory T cell differentiation via the upregulation of indoleamine 2,3-dioxygenase: novel pharmacological strategies for augmenting immunotherapy efficacy.
Holtzhausen, A., Zhao, F. Evans, K., Orabona, C., Hanks, B.
(2014) Journal for ImmunoTherapy of Cancer. 2(Suppl 3):P209 (6 November 2014).
Combinatorial TGF-β signaling blockade and anti-CTLA-4 antibody immunotherapy in a murine BRAFV600E-PTEN-/- transgenic model of melanoma.
Holtzhausen, A., Evans, K., Siska, P., Rathmell, J., and Hanks, B.
(2014) Journal of Clinical Oncology. 32:5s. (suppl; abstr 3011).
Role of the Wnt-β-catenin Signaling Pathway in Melanoma-mediated Dendritic Cell Tolerization.
Holtzhausen, A., Evans, K., and Hanks, B.
(2013) Journal for ImmunoTherapy of Cancer.1: 153. (suppl 1).
Effect of the loss of the type III TGFβ receptor during tumor progression on tumor microenvironment: Preclinical development of TGFβ inhibition and TGFβ-related biomarkers to enhance immunotherapy efficacy.
Hanks, B.A., Holtzhausen, A., Gimpel, P, Jamieson, P. Campbell, O., Sun, L., Augustine, C.K.,
Tyler, T.S., Osada, T., Morse, M., Ling, L.E., Lyerly, H.K. and Blobe, G.C.;
(2012) Journal of Clinical Oncology. 30. (suppl; abstr 10563).
Lab Members
Principal Investigator
Medical Instructor
Lab Manager
Post-doctoral Associate
Research Technician
Post-doctoral Associate
Undergraduate Researcher
Lab Alumni
Undergraduate Researcher
2017-2018
Research Technician II
2015-2018
Post-doctoral Associate
2014-2018