HANKS LAB


Tumor Immunology and Immunotherapy

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:

  1. Elucidating mechanisms of tumor-induced dendritic cell tolerization and immune suppression
    1. Investigating cancer-mediated paracrine signaling pathways and cancer-derived exosome-dependent pathways that functionally tolerize dendritic cells within the tumor microenvironment.
    2. Understanding the metabolic shifts of dendritic cells within the tumor microenvironment that enable the development of regulatory T cells.
    3. Characterizing novel pathways of regulating indoleamine 2,3-dioxygenase enzyme activity in the cancer microenvironment
  2. Investigating mechanisms of immunotherapy resistance in melanoma, non-small cell lung cancer, and colon cancer based on both transgenic model systems as well as clinic specimens derived from ongoing clinical trial protocols.
  3. Understanding the role of cancer-associated fibroblasts in the generation of an immunotolerant tumor microenvironment.
  4. Development of novel dendritic cell-based cancer vaccine and oncolytic virus immunotherapy strategies.




Lab Updates

  • trending_upMichael Plebanek joins the Hanks Lab!

    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.

  • trending_up Michael Sturdivant joins the Hanks Lab!

    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!

  • local_atm The Hanks Lab receives funding from D3 A*STAR and Tempest Therapeutics

    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.

  • trending_up Michelle Dantzler joins the Hanks Lab!

    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.

  • thumb_upThe Hanks Lab receives a 3 year pre-clinical research grant from Merck

    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.

  • whatshotDr. DeVito receives the 2018 Damon Runyon Physician Scientist Training Award

    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.

  • thumb_upThe Hanks Lab receives a two year award from Merck

    The Hanks Lab receives a 2 year award from Merck to investigate novel biomarkers of immunotherapy resistance in advanced melanoma. Please see the following link: http://www.dukecancerinstitute.org/news/hanks-team-awarded-500000-study-immunotherapy-resistance

  • whatshotDr. DeVito receives awarded a 2017 ASCO Conquer Cancer Foundation Young Investigator Award

    Dr. DeVito was awarded the 2017 American Society Clinical Oncology (ASCO) Conquer Cancer Foundation Young Investigator Award for his ongoing work investigating the role of oncogenic signaling pathways in the immune tolerization of the melanoma microenvironment. Dr. DeVito will receive this one year award during a ceremony at the 2017 ASCO Annual Meeting in Chicago in early June.

  • thumb_upThe Hanks Lab receives a two year 2017 Pilot Award from the Melanoma Research Alliance

    The Hanks Lab has been awarded a two year award to continue their investigation into mechanisms of checkpoint inhibitor resistance in pre-clinical transgenic models of melanoma.

  • whatshotDr. DeVito receives the 2017 2nd Year Hem/Onc Fellows Research Presentation Award

    Dr. DeVito was awarded the 2nd Year Fellows Research Presentation Award for his talk ‘Inhibiting Paracrine Wnt-Beta-catenin Signaling to Augment the Efficacy of Anti-PD-1 Antibody Immunotherapy in Melanoma’ at the 2017 Annual Hematology/Oncology Fellows Research Retreat!

Publications

Stromal Fibroblasts Mediate Anti–PD-1 Resistance via MMP-9 and Dictate TGFβ Inhibitor Sequencing in Melanoma
Zhao, F., Evans, K., Xiao, C., DeVito, N., Theivanthiran, B., Holtzhausen, A., Siska, P.J., Blobe, G.C., and Hanks, B.A.
(2018) Cancer Immunology Research. 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

Brent Hanks, M.D., Ph.D.

Principal Investigator

Nicholas DeVito, M.D.

Medical Instructor

Kathy Evans, B.S.

Lab Manager

Michael Plebanek, Ph.D.

Post-doctoral Associate

Michael Sturdivant, B.S.

Research Technician

Bala Theivanthiran, Ph.D.

Post-doctoral Associate

Michelle Dantzler

Undergraduate Researcher

Lab Alumni

Nick Jerles

Undergraduate Researcher

2017-2018

Christine Xiao, BS

Research Technician II

2015-2018

Fei Zhao, Ph.D.

Post-doctoral Associate

2014-2018