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 immunotherapies while also developing predictive biomarkers to better guide the management of cancer patients with these agents. We strive to translate our understanding of the fundamental biochemical and metabolic pathways within the tumor microenvironment that are critical for driving immune evasion and resistance into early phase clinical trial testing.

Research

Our work utilizes a variety of techniques and methodologies that span the breadth of basic biological research. This work integrates studies based on both 1) transgenic mouse tumor models that are monitored using bioluminescence and micro-CT imaging, 2) a variety of clinical specimens, and 3) various bioinformatic approaches.

Our current areas of focus include:

  1. Investigating mechanisms of adaptive or acquired immunotherapy resistance in cancer
  2. Elucidating mechanisms of dendritic cell tolerization in the tumor microenvironment and how these processes may contribute to immunotherapy resistance
  3. Understanding the underlying mechanisms involved in EMT-associated tumor immune evasion
  4. Development of novel pharmacologic and genetic strategies to overcome immunotherapy resistance
  5. Investigating mechanisms contributing to select immunotherapy-associated toxicities


Lab Updates

  • local_atmHanks Lab Receives 2022 Melanoma Research Foundation Grant!

    Based on work led by Dr. Nick DeVito, this award will support for studies focused on the role of the Gli2 pathway in immune evasion and immunotherapy resistance in melanoma.
    https://melanoma.org/funded-research/role-of-the-gli2-pathway-in-melanoma-immunotherapy-resistance

  • celebrationHanks Lab Receives 2022 Cancer Research Institute Clinical and Laboratory Integration Program Award!

    Based on work led by Dr. Bala Thievanthiran, this funding will support further studies investigating the underlying mechanisms of immunotherapy-associated toxicities. https://www.cancerresearch.org/cri-funded-scientists/brent-a-hanks-m-d-ph-d

  • trending_upKaylee Howell, B.S. joins the Hanks Lab!

    Kaylee has joined the Hanks Lab to support many aspects of lab operations including clinical specimen acquisition and processing as well as mouse breeding and colony management. She will also be taking an active role in studies related to the Gli2 pathway in immune evasion as well as on the role of various inflammasomes in driving immunotherapy resistance.

  • trending_upYue Xue, Ph.D. joins the Hanks Lab!

    We are delighted that Dr. Xue is joining the Hanks Lab to support and extend our studies focused on understanding how cancers suppress anti-tumor immunity by inducing dendritic cell tolerization.

  • whatshotNick DeVito, M.D. receives a 2022 Strong Start Award!

    Dr. DeVito has received a 3-year Strong Start Award from the Duke School of Medicine to support ongoing studies focused on the role of EMT in driving immune evasion and immunotherapy resistance in colon cancer

  • whatshot Michael Plebanek, Ph.D. receives the 2021 Duke Cancer Institute Research Retreat Bell Award!

    Dr. Michael Plebanek was awarded the 2021 Duke Cancer Institute Research Retreat Bell Award for his work on characterizing a novel population of tolerogenic dendritic cells associated with a variety of cancers

  • whatshot Nick DeVito, M.D. receives a 2021 Fund to Retain Physician Scientists Award!

    The 2021 Fund to Retain Physician Scientists Award will support ongoing work examining the role of EMT in tumor-mediated immune evasion.

  • whatshot Bala Thievanthiran, Ph.D. receives a 2021 NIH/NCI Diversity Supplement Award!

    Dr. Thievanthiran was awarded a 2021 NIH/NCI Diversity Supplement Award to support his ongoing work characterizing a tumor-intrinsic adaptive resistance pathway to anti-PD-1 immunotherapy involving the NLRP3 inflammasome.

  • trending_up Nagendra Yarla, Ph.D. joins the Hanks Lab!

    Dr. Yarla will be expanding the labs' efforts in investigating immunotherapy resistance mechanisms in melanoma and the gastrointestinal malignancies.

  • trending_up Linda Cao joins the Hanks Lab!

    Linda is currently a Duke undergraduate student in the Biology and Global Health Programs. She will provide key support to the lab while also spearheading her own project in tumor immunology.

  • trending_up Y-Van Nguyen, B.S. joins the Hanks Lab!

    Y-Van is a recent graduate from the Biology program at University of North Carolina - Chapel Hill. She will play a major role in supporting our work in tumor-mediated dendritic cell tolerogenesis.

  • local_atm The Hanks Lab receives ASCO/CCF funding!

    The Hanks Lab has been awarded the 2021 Advanced Clinical Research Award in Tumor Immunotherapy to investigate the role of the tumor NLRP3 inflammasome in immunotherapy resistance based on an upcoming investigator-initiated clinical trial in anti-PD-1-resistant melanoma conducted in collaboration with Dr. April Salama.

Publications

Tumor-intrinsic NLRP3-HSP70-TLR4 axis drives premetastatic niche development and hyperprogression during anti-PD-1 immunotherapy. Theivanthiran, B, Yarla, N, Haykal, T, Nguyen, Y.V, Cao L, Ferreira, M, Holtzhausen, A, Al-Rohil, R, Salama, A.K.S, Beasley, G.M, Plebanek, M.P, DeVito, N.C, Hanks, B.A. (2022) Science Translational Medicine. Nov 14(672):eabq7019. doi: 10.1126/scitranslmed.abq7019. PMID: 36417489.
Multicenter Experience with Neoadjuvant Therapy in Melanoma Highlights Heterogeneity in Contemporary Practice. Rhodin, K.E, Gaughan, E.M, Raman, V, Salama, A.K, Hanks, B.A, Shah, R, Tyler, D.S, Slingluff, C.L Jr, Beasley, G.M. (2022) Ann Surg. Jul 7. doi: 10.1097/SLA.0000000000005459. PMID: 35797609.
The "Inside" Story on Tumor-Expressed PD-L1. Hanks, B.A. (2022) Cancer Res. Jun 82(11):2069-2071. doi: 10.1158/0008-5472.CAN-22-1060. PMID: 35661198.
Identification of a Germline Pyrin Variant in a Metastatic Melanoma Patient With Multiple Spontaneous Regressions and Immune-related Adverse Events. Oswalt, C.J, Al-Rohil, R.N, Theivanthiran, B, Haykal, T, Salama, A.K.S, DeVito, N.C, Holtzhausen, A, Ko, D.C, Hanks, B.A. (2022) J Immunother. Jul-Aug 45(6):284-290. doi: 10.1097/CJI.0000000000000425. PMID: 35621992.
APOBEC mutagenesis inhibits breast cancer growth through induction of a T cell-mediated anti-tumor immune response. DiMarco, A.V, Qin, X, McKinney, B, Garcia, N.M.G, Van Alsten, S.C, Mendes, E.A, Force, J, Hanks, B.A, Troester, M.A, Owzar, K, Xie, J, Alvarez, J. (2022) Cancer Immunol Res. Jan 10(1):70-86. doi: 10.1158/2326-6066.CIR-21-0146. PMID: 34795033.
Overcoming Immunotherapy Resistance by Targeting the Tumor-Intrinsic NLRP3-HSP70 Signaling Axis. Theivanthiran, B, Haykal, T, Cao, L, Holtzhausen, A, Plebanek, M, DeVito, N, Hanks, B.A. (2021) Cancers. Oct 12. doi: 10.3390/cancers13194753. PMID: 34638239.
Inhibition of estrogen signaling in myeloid cells increases tumor immunity in melanoma. Chakraborty, B, Byemerwa, J, Shepherd, J, Haines, C, Baldi, R, Gong, W, Liu, W, Mukherjee, D, Artham, S, Lim, F, Bae, Y, Brueckner, O, Tavares, K, Wardell, S, Hanks, B.A, Perou, C, Chang, C-Y, McDonnell, D.P. (2021) J Clinical Investigation. Oct 12:e151347. 10.1172/JCI151347. PMID: 34637400.
Clinical Trials with Biological Endpoints in Immuno-Oncology: Concepts and Usage. Isaacs, J, Tan, A, Hanks, B.A, Wang, X, Owzar, K, Herndon, J.E, Antonia, S.J, Piantadosi, S, Khasraw, M. (2021) Clin Cancer Res. Jul 26. 10.1158/1078-0432.CCR-21-1593. PMID: 34312214.
Pharmacological Wnt Ligand Inhibition Overcomes Key Tumor-mediated Resistance Pathways to Anti-PD-1 Checkpoint Inhibitor Immunotherapy. DeVito, N, Sturdivant, M, Xiao, C, Theivanthiran, B, Plebanek, M, Salama, A.K.S, Beasley, G.M, Hotlzhausen, A, Novotny-Diermayr, V, Strickler, J.M, Hanks, B.A. (2021) Cell Reports. 35(5): 109071. doi: 10.1016/j.celrep.2021.109071. PMID: 33951424.
Three-year survival, correlates and salvage therapies in patients receiving first-line pembrolizumab for advanced Merkel cell carcinoma. Nghiem, P, Bhatia, S, Lipson, E, Sharfman, W, Kudchadkar, R, Brohl, A, Friedlander, P, Daud, A, Kluger, H, Reddy, S, Boulmay, B, Riker, A, Burgess, M, Hanks, B.A, Olencki, T, Kendra, K, Church, C, Akaike, T, Ramchurren, N, Shinohara, M, Salim, B, Taube, J, Jensen, E, Kalabis, M, Fling, S, Moreno, B, Sharon, E, Cheever, M, Topalian, S. (2021) ImmunoTherapy of Cancer. 9(4): e002478. April. doi: 10.1136/jit-2021-002478. PMID: 33879601.
The State of Melanoma: Emergent Challenges and Opportunities. Atkins, M.B, Fisher, D.E, Tsao, H, Gerhsenwald, J.E, Grossman, D, Curiel-Lewandrowski, C, Leachman, S.A, Ferris, L.K, Nelson, K.C, Jeter, J.M, Swetter, S.M, Aguirre-Ghiso, J.A, Weeraratna, A.T, Soengas, M.S, Hernando, E, Sullivan, R.J, Herlyn, M, Flaherty, K, Tawbi, H.A, Sosman, J.A, Fox, B.A, Hanks, B.A, Khleif, S.N, Daud, A.I, Chapman, P.B, Sondak, V.K, Chandra, S, Kirkwood, J.M, Johnson, D.J, Eroglu, Z, Pavlick, A.C, Gibney, G.T, Mays, D, Cassidy, P.B, Hanniford, D, Merlino, G. (2021) Clin Cancer Res. Jan 7. doi: 10.1158/1078-0432.CCR-20-4092. PMID: 33414132.
Flt3 Ligand Significantly Augments Immune Responses to a Dendritic Cell Targeting anti-DEC-205-NY-ESO-1 Vaccine through Expansion of Dendritic Cell Subsets. Bhardwaj, N, Friedlander, P, Pavlick, A, Ernstoff, M, Gastman, B, Hanks, B.A, Curti, B, Albertini, M.R, Luke, J, Blazquez, A, Balan, S, Bedognetti, D, Beechem, J, Crocker, A, D’Amico, L, Danaher, P, Davis, T, Hawthorne, T, Hess, B, Keler, T, Lundgren, L, Morishima, C, Ramchurren, N, Rinchai, D, Salazar, A, Salim, B, Sharon, E, Wang, E, Warren, S, Yellin, M, Disis, M, Cheever, M, Fling, S. (2020) Nature Cancer. 1: 1204-1217. November 16, 2020.
SITC Cancer Immunotherapy Biomarkers Resource Document: Resources and Useful Tools - A Compass in the Land of Biomarker Discovery. Hu-Lieskovan, S, Bhaumik, S, Dhodapkar, K, Grivel, J.C, Gupta, S, Hanks, B.A, Janetski, S, Kleen, T.O, Koguchi, Y, Lund, A, Maccalli, C, Mahnke, Y, Novosaidly, R, Selvan, S, Sims, T, Zhao, Y, Maeker, H.T. (2020) J ImmunoTherapy of Cancer. 8(2):e000705. doi: 10.1136/jitc-2020-000705. PMID: 33268350.
Tumor Mutational Burden as a Predictor of Immunotherapy Response: Is More Always Better. Strickler, J.H, Hanks, B.A, Khasraw, M. (2020) Clin Cancer Res. Nov 16:clinccanres.3054.2020. doi:10.1158/1078-0432.CCR-20-3054. PMID: 33199494.
Ipilimumab and Radiation in Patients with High Risk Resected or Regionally Advanced Melanoma. Salama, A.K.S, Palta, M, Rushing, C.N, Selim, M.A, Lineey, K.N, Czito, B.G, Yoo, D.S, Hanks, B.A, Beasley, G.M, Mosca, P, Dumbauld, C, Steadman, K.N, Yi, J.S, Weinhold, K.J, Tyler, D.S, Lee, W.T, Brizel, D.M. (2020) Clin Cancer Res. Nov 10:clincancres.2452.2020. doi: 10.1158/1078-0432.CCR-20-2452. PMID: 33172894.
Higher BMI, but not sarcopenia, is associated with pembrolizumab-related toxicity in patients with advanced melanoma. Hu, J.B, Ravichandran, S, Rushing, C, Beasley, G.M, Hanks, B.A, Jung, S.H, Salama, A.K.S, Ho, L, Mosca, P.J. (2020) Anticancer Res. 0(9): 5245-5254. doi: 10.21873/anticanres.14528. PMID: 32878813.
Dissecting the immune landscape of tumor draining lymph nodes in melanoma with high-plex spatially resolved protein detection. Beasley, G.M, Therien, A.D, Holl, E.K, Al-Rohil, R, Selim, M.A, Farrow, N.E, Pan, L, Haynes, P, Tyler, D.S, Hanks, B.A, Nair, S.K. (2020) Cancer Immunol Immunother. Aug 19. doi: 10.1007/s00262-020-02698-2. PMID: 32814992.
Role of Dendritic Cell Metabolic Reprograming in Tumor Immune Evasion. Plebanek, M, Sturdivant, M, DeVito, N, Hanks, B.A. (2020) International Journal Immunology. May 25. doi: 10.1093/intimm/dxaa036. PMID: 32449776.
A Tumor-intrinsic PD-L1-NLRP3 Inflammasome Signaling Pathway Drives Resistance to Anti-PD-1 Immunotherapy. Theivanthiran, B, Evans, K, DeVito, N, Plebanek, M, Sturdivant, M, Holtzhausen, A, Wachsmuth, L.P, Salama, A.K.S, Kang, Y, Hsu, D, Star, M, Nixon, A, Hanks, B.A. (2020) Journal of Clinical Investigation. Pii: 133055. doi: 10.1172/JCI133055. PMID: 31921140.
Role of Tumor-Mediated Dendritic Cell Tolerization in Immune Evasion. DeVito NC, Plebanek MP, Theivanthiran B, Hanks BA. (2019) Front Immunol. Dec 10;10:2876. doi: 10.3389/fimmu.2019.02876. eCollection 2019. PMID: 31921140.
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, Hanks, B.A. (2018) Cancer Immunology Research. 6(12): 1459-1471. Sept doi: 10.1158/2326-6066.CIR-18-0086. PMID: 30209062.
Editorials:
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, Hanks, B.A. (2018) Immunity. 548(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, 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, Hanks, B.A. (2016) J ImmunoTherapy of Cancer. 94:89. 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.S, Tsutsui M, Orabona C, Tyler D.S, 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, 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, Hanks B.A. (2014) Front Immunol. 5:438. doi: 10.3389/fimmu.2014.00438. eCollection 2014. PMID: 25339948.
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, 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. 1(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

A Tumor-Lung NLRP3-TLR4 Distant Signaling Axis Drives Immunotherapy Resistance via G-CSF-dependent Expansion of Circulating PD-1+ PMN-MDSCs. Theivanthiran, B, Yarla, N, Haykal, T, DeVito, N, Plebanek, M, Cao, L, Nguyen, Y, Hanks, B.A. (2022) 2022 SITC Annual Meeting. Abstract #533. November 10, 2022 Poster Presentation.
Overcoming Hedgehog-mediated Anti-PD-1 Resistance in Melanoma through Prostaglandin Inhibition. DeVito, N.C, Sturdivant, M, Nguyen, Y, Plebanek, M, Aksu, M, Jain, V, Theivanthiran, B, Francica, B, Dubensky, T, Hanks, B.A. (2022) 2022 SITC Annual Meeting. Abstract #513. November 10, 2022 Poster Presentation.
Activity of the Tumor-intrinsic NLRP3 Inflammasome Pathway Predicts for Response to Checkpoint Inhibitor Immunotherapy in Melanoma Patients. Haykal, T, Yarla, N, DeVito, N, Beasley, G, Salama, A.K.S, Theivanthiran, B, Hanks, B.A. (2022) 2022 SITC Annual Meeting. Abstract #22. November 11, 2022 Poster Presentation.
The Role of Combination Immune Checkpoint Inhibitors as Salvage Therapy for PD-1/PD-L1-resistant Merkel Cell Carcinoma. Haykal, T, Beasley, G, Salama, A.K.S, Hanks, B.A. (2022) 2022 SITC Annual Meeting. Abstract #827. November 10, 2022 Poster Presentation.
The Tumor-intrinsic NLRP3 Inflammasome Establishes a Pulmonary Metastatic Niche via Type II Epithelial HSP70/TLR4 Signaling and Facilitates Disease Hyperprogression in Response to Immunotherapy. Theivanthiran, B, Liu, F, DeVito, N.C, Plebanek, M.P, Hanks, B.A. (2021) 2021 SITC Annual Meeting. Abstract #15872. November 13, 2021 Poster Presentation.
Characterization and Therapeutic Targeting of a Tumor-associated Tolerogenic DC Subpopulation Driven by SREBP2 and the Mevalonate Metabolic Pathway. Plebanek, M, DeVito, N, Liu, F, Theivanthiran, B, Beasley, G.M, Hanks, B.A. (2021) 2021 SITC Annual Meeting. Abstract #15469. November 13, 2021 Poster Presentation.
Hedgehog Signaling Drives Epithelial-to-Mesenchymal Transition, Immune Evasion, and Anti-PD-1 Resistance through Upregulation of Wnt Ligand and PGE2 Synthesis. DeVito, N.C, Sturdivant, M, Nguyen, Y, Plebanek, M, Theivanthiran, B, Liu, F, Hanks, B.A. (2021) 2021 SITC Annual Meeting. Abstract #15280. November 13, 2021 Poster Presentation.
The Tumor-intrinsic PD-L1-NLRP3 Inflammasome Signaling Axis: Opportunities for Improving Immunotherapy Outcomes in Cancer. Hanks, B.A. (2021) Hematology-Oncology Grand Rounds Cutter Lecture Series. Vanderbilt University Medical Center. Nashville, TN. October 25, 2021 Virtual Presentation.
The Tumor-intrinsic PD-L1-NLRP3 Inflammasome Signaling Axis: Opportunities for Improving Immunotherapy Outcomes in Cancer. Hanks, B.A. (2021) Kemp Cease Hematology-Oncology Research Conference. University of Michigan School of Medicine. Ann Arbor, Michigan. October 19, 2021 Virtual Presentation.
Role of the Tumor-intrinsic PD-L1-NLRP3 Inflammasome Signaling Axis in Adaptive Resistance to Immunotherapy. Hanks, B. (2021) 8th European Immunotherapy of Cancer Conference (iTOC8) Annual Meeting. Munich, Germany October, 8, 2021 Virtual Presentation.
Investigation of Wnt Ligand Signaling Regulators as a Predictor of Anti-PD-1 Response in Metastatic Melanoma. DeVito, N.C, Sturdivant, M, Wachsmuth, L.P, Strickler, J.H, Beasley, G, Al-Rohil, R, Salama, A.K.S, Hanks, B.A. (2020) SITC Annual Virtual Meeting. Abstract #P425. Poster Presentation.
Targeting a Tumor Intrinsic PD-L1-NLRP3 Signaling Pathway to Overcome Adaptive Resistance to Anti-PD-1 Antibody Immunotherapy. Hanks, B.A. (2020) Immuno-Oncology Virtual Summit. October 20, 2020
Rise of the Machines: AI in Predicting Immunotherapy Outcomes. Hanks, B.A. (2019) Annual ASCO Virtual Meeting. Clinical Science Symposium.
Tumor-mediated Dendritic Cell Tolerization via Metabolic Reprogramming. Hanks, B.A. (2019) Japanese Society of Immunology Annual Meeting. Hamamatsu, Japan. December 10, 2019
A Tumor PD-L1-NLRP3-TLR4 Signaling Pathway Drives Adaptive Resistance to Anti-PD-1 Immunotherapy. Theivanthiran, B, Evans, K.S, DeVito, N.C, Plebanek, M, Sturdivant, M, Holtzhausen, A, Wachsmuth, L, Salama, A.K.S, Kang, Y, Hsu, D, Balko, D, Johnson, D.B, Starr,M, Nixon, A, Hanks, B.A. (2019) SITC Annual Meeting. Washington, DC. Abstract #P541. November 8, 2019 Poster Presentation.
Targeting Wnt Ligand Signaling as a Strategy for Overcoming Resistance to Anti-PD-1 Antibody Immunotherapy. Hanks, B. (2019) Immuno-Oncology Summit. Boston, MA. August 5, 2019
Blockade of the PPARα metabolic checkpoint with TPST-1120 suppresses tumor growth and stimulates anti-tumor immunity. Whiting, C, Stock, N, Messmer, D, Chen, A, Rahbaek, L, Metzger, D, Enstrom, A, Sturdivant, M, DeVito, N, Spaner, D, Prasit, P, Hanks, B.A, Panigrahy, D, Laport, G. (2019) AACR Annual Meeting. Atlanta, GA. March 29, 2019
Melanoma Research: Where we have been and where we are going. Hanks, B.A. (2019) Melanoma Research Alliance Annual Meeting. Washington, DC. February 25, 2019 Patient Forum.
Inflammasome-Wnt Ligand Signaling Axis Promotes Immune Escape During Anti-PD-1 Antibody Immunotherapy. Theivanthiran, B, DeVito, N, Evans, K, Sturdivant, M, Plebanek, M, Holtzhausen, A, Hsu, D, Lewicki, J, Hanks, B.A. (2018) SITC Annual Meeting. Washington, DC. Abstract #10539. November 7, 2018 Oral Presentation.
Durable tumor regression and overall survival (OS) in patients with advanced Merkel cell carcinoma (aMCC) receiving pembrolizumab as first-line therapy. Nghiem, P, Bhatia, S, Lipson, E, Sharfman, W.H, Kudchadkar, R.R, Friedlander, P.A, Brohl, A.S, Daud, A, Kluger, H, Reddy, S, Burgess, M, Hanks, B.A, Olencki, T, Boulmay, B.C, Lundgren, L.M, Ramchurren, N, Moreno, B.H, Sharon, E, Cheever, M.A, Topalian, S.L. (2018) ASCO Annual Meeting. Chicago, IL. Abstract #9506. June 1, 2018 Oral Presentation.
Pilot trial of an Indoleamine 2,3-dioxygenase-1 (IDO1) inhibitor plus a multipeptide melanoma vaccine in patients with advanced melanoma. Slingluff Jr. C, Fling,S, Mauldin, I. Ernstoff, M.S, Hanks, B.A, Delman, K.A, Lawson, D.A, Gastman, B, Kaiser, J.C, Cheever, M.A. (2018) ASCO Annual Meeting. Chicago, IL. Abstract #3033. June 1, 2018 Poster Presentation.
Tumor-mediated Modulation of Immunometabolism as a Mechanism of Immunotherapy Resistance. Hanks, B. (2018) Immuno-Oncology Summit. Boston, MA. August 27, 2018
Investigating the Role of Innate Immunity in Adaptive Resistance to Cancer Immunotherapy. Hanks, B. (2018) Biomarkers and Immuno-Oncology World Congress. Boston, MA. June 13, 2018
Role of the Wnt-β-catenin Signaling Pathway in Tumor-mediated Immune Evasion and Immunotherapy Resistance. Hanks, B. (2018) Duke-NUS. Singapore. March 27, 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, Hanks, B. (2017) Journal for Immunotherapy of Cancer. Washington, DC. 5(Suppl 2): P385. November 8, 2017 Poster Presentation.
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, Hanks, B. (2017) Journal of Clinical Oncology. Chicago, IL. 35: (suppl; abstract 3053). Poster Presentation.
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. Washington, DC. Oral Presentation.
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. Chicago, IL. June 2, 2017 Oral Presentation.
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, Hanks, B. (2016) Journal for ImmunoTherapy of Cancer. Washington, DC. 4(Suppl 1): O11. November 9, 2016 Oral Presentation.
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, Fling, S. (2016) Journal for ImmunoTherapy of Cancer. Washington, DC. 4(Suppl 1):P166. Poster Presentation.
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, Hanks, B.A. (2016) Journal for ImmunoTherapy of Cancer. Washington, DC. 4(Suppl 1):P383. November, 11 2016 Poster Presentation.
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, Fling, S. (2016) Journal of Clinical Oncology. Chicago, IL. 34: (suppl; abstr 9589). Poster Presentation.
Tumor-mediated Metabolic Re-Programing of Dendritic Cells as a Fundamental Mechanism of Immune Tolerance and Immunotherapy Resistance. Zhao, F, Evans, K, Xiao, C. Hanks, B.A. (2016) Keystone Symposium: Immunometabolism. Banff, Alberta, Canada. February 25, 2016
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, 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 November, 6 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, 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, 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, Blobe, G.C. (2012) Journal of Clinical Oncology. 30. (suppl; abstr 10563).

Ongoing Clinical Trials

DREAM Trial for Immunotherapy-resistant Advanced Melanoma Patients

The Hanks Lab has initiated an interventional trial for advanced melanoma patients that are refractory to standard-of-care immunotherapy options including pembrolizumab (Keytruda) and nivolumab (Opdivo).
Duke Trial Information: DREAM Trial for Immunotherapy-resistant Advanced Melanoma Patients
NIH Clinical Trial: Study of Dapansutrile Plus Pembrolizumab in Patients With PD-1 Refractory Advanced Melanoma

Understanding Immunotherapy Resistance Mechanisms in Advanced Melanoma

The goal of this study is to identify biomarkers of immunotherapy resistance in patients with unresectable or metastatic melanoma. By analyzing data from patients, the Hanks lab can develop pre-clinical models to overcome immunotherapy resistance.
NIH Clinical Trial: Understanding Immunotherapy Resistance Mechanisms in Advanced Melanoma

IMBARC: A Study to Investigate Biomarkers of Immunotherapy Related Adverse Events

The Hanks Labs is leading a prospective study to evaluate immune-related adverse events and associated biomarkers in patients receiving immunotherapy for cancer.

PAIR-MSI: Features of Primary and Adaptive Immunotherapy Resistance in Microsatellite Instable Cancers

The purpose of this study is to identify clinical, genomic, and transcriptomic features of primary and adaptive resistance to immunotherapy treatment in metastatic (Stage IV) Microsatellite Instable (MSI-H/dMMR) or Tumor Mutational Burden (TMB)-High tumors from patients with endometrial, prostate, breast, and gastrointestinal (GI) cancers.
Duke Trial Information: Features of Primary and Adaptive Immunotherapy Resistance in Microsatellite Instable Cancers

info If you are interested in additional information for these clinical trials or would like to inquire about other open trials, please contact the Melanoma Clinical Trials Office at 919-613-0400.

Lab Members

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

Principal Investigator

[email protected]
Nicholas DeVito, M.D.

Medical Instructor

[email protected]
Bala Theivanthiran, Ph.D.

Research Scientist

[email protected]
Michael Plebanek, Ph.D.

Post-doctoral Associate

[email protected]
Y-Van Nguyen, B.S.

Laboratory Research Analyst I

[email protected]
Nagendra Yarla, Ph.D.

Post-Doctoral Associate

[email protected]
Yue Xue, PhD.

Post-doctoral Associate

[email protected]
Mandy Wang, B.S.

Graduate Student

[email protected]
Kaylee Howell, B.S.

Research Technician I

[email protected]
Linda Cao

Undergraduate Researcher

Lab Alumni

Hyung Soon Park, M.D

Visiting Scholar

2021 - 2022

Michelle Dantzler, B.S.

Undergraduate Researcher

2018 - 2021

Michael Sturdivant, B.S.

Research Technician

2018 - 2020

Li Lu, M.D.

Visiting Scholar

2019 - 2020

Kathy Evans, B.S.

Lab Manager

2013 - 2020

Christine Xiao, BS

Research Technician II

2015 - 2018

Nick Jerles

Undergraduate Researcher

2017 - 2018

Fei Zhao, Ph.D.

Post-doctoral Associate

2014 - 2018