Research Summary

Immunotherapy for melanoma and hepatocellular cancer has been my research focus since 1995. My team has performed human translational research and utilized cancer vaccination (with peptides, proteins, adenoviruses and dendritic cells (DC)) to promote antitumor immunity. My lab has placed importance upon careful analysis of the lymphocytes specific for tumor to understand the tumor-immune system interplay, and the effects of vaccination. Our current basic research is investigating the effects of antigen sources on DC and resultant T cell and NK cell activation. From our recently completed DC vaccine trial in melanoma, we are analyzing critical molecules and pathways in the DC vaccines, T and NK cells that impact optimal antitumor immunity.

We are investigating critical molecules and pathways in human DC that are important for effector cell activation and improved outcomes in patients, including CTLA-4, PD-L1 and ICOSL as well as cellular metabolism. We are also investigating key suppressive mechanisms involving the hepatocellular cancer-secreted molecule AFP, which negatively impacts DC metabolism and activity.

My team science work has been to help develop novel cellular therapeutics and monitor immunotherapy clinical trials with many collaborators. As a leader in the Society for Immunotherapy of Cancer (SITC), including society President (2017-2018), I have been involved in many cancer immunotherapy field-wide initiatives, including around biomarkers. I have published over 160 peer-reviewed manuscripts and mentored over 20 graduate students and postdoctoral fellows.

Education

Rensselaer Polytechnic Institute, Troy, New York, B.S., 05/86, Biology
University of California Los Angeles, Ph.D., 02/93, Biology
University of California Los Angeles, Postdoc fellow, 03/95, Tumor Immunology
University of California Los Angeles, Postdoc fellow, 03/97, Radiation Oncology

Honors & Awards

  • 2010-2014
    Standing member, NIH CII Study Section, Cancer Immunopathology and Immunotherapy
  • 2010
    iSBTc Team Science Recognition Award
  • 2011-present
    Editorial Board, OncoImmunology
  • 2012-2019
    Section Editor, Journal of ImmunoTherapy of Cancer; Immunotherapy Biomarkers section
  • 2016
    AAI Travel Award to the International Congress on Immunology, Melbourne, Australia
  • 2016-2023
    Member, Food and Drug Administration Cellular, Tissues and Gene Therapies Advisory Committee
  • 2018-3/2023
    Chair, Food and Drug Administration Cellular, Tissues and Gene Therapies Advisory Committee
  • 2017-2019
    Member, FNIH Drug Selection Committee for the Lung-MAP Clinical Trial
  • 2017-2018
    Member, AACR Education Committee for the 2018 Annual Meeting
  • 2019-present
    Member, PICI Scholars and Fellows Scientific Review Committee
  • 2020-present
    Member, PICI Invention Review Committee
  • 2020
    Member, PICI Revenue Initiative Committee

Selected Publications

  1. Hodi FS, Lee S, McDermott DF, Rao UN, Butterfield LH, Tarhini AA, Leming P, Puzanov I, Shin D, Kirkwood JM. Ipilimumab plus sargramostim vs ipilimumab alone for treatment of metastatic melanoma: a randomized clinical trial. JAMA. 2014 Nov 5;312(17):1744-53.
    View on PubMed
  2. Pardee AD, Shi J, Butterfield LH. Tumor-derived α-fetoprotein impairs the differentiation and T cell stimulatory activity of human dendritic cells. J Immunol. 2014 Dec 1;193(11):5723-32.
    View on PubMed
  3. Vujanovic L, Shi J, Kirkwood JM, Storkus WJ, Butterfield LH. Molecular mimicry of MAGE-A6 and Mycoplasma penetrans HF-2 epitopes in the induction of antitumor CD8+ T-cell responses. Oncoimmunology. 2014 Nov 14;3(8):e954501.
    View on PubMed
  4. Okada H, Butterfield LH, Hamilton RL, Hoji A, Sakaki M, Ahn BJ, Kohanbash G, Drappatz J, Engh J, Amankulor N, Lively MO, Chan MD, Salazar AM, Shaw EG, Potter DM, Lieberman FS. Induction of robust type-I CD8+ T-cell responses in WHO grade 2 low-grade glioma patients receiving peptide-based vaccines in combination with poly-ICLC. Clin Cancer Res. 2015 Jan 15;21(2):286-94.
    View on PubMed
  5. Pardee AD, Yano H, Weinstein AM, Ponce AA, Ethridge AD, Normolle DP, Vujanovic L, Mizejewski GJ, Watkins SC, Butterfield LH. Route of antigen delivery impacts the immunostimulatory activity of dendritic cell-based vaccines for hepatocellular carcinoma. J Immunother Cancer. 2015 Jul 21;3:32.
    View on PubMed
  6. Vujanovic L, Stahl EC, Pardee AD, Geller DA, Tsung A, Watkins SC, Gibson GA, Storkus WJ, Butterfield LH. Tumor-Derived α-Fetoprotein Directly Drives Human Natural Killer-Cell Activation and Subsequent Cell Death. Cancer Immunol Res. 2017 Jun;5(6):493-502.
    View on PubMed
  7. Butterfield LH, Zhao F, Lee S, Tarhini AA, Margolin KA, White RL, Atkins MB, Cohen GI, Whiteside TL, Kirkwood JM, Lawson DH. Immune Correlates of GM-CSF and Melanoma Peptide Vaccination in a Randomized Trial for the Adjuvant Therapy of Resected High-Risk Melanoma (E4697). Clin Cancer Res. 2017 Sep 1;23(17):5034-5043.
    View on PubMed
  8. Zhou J, Mahoney KM, Giobbie-Hurder A, Zhao F, Lee S, Liao X, Rodig S, Li J, Wu X, Butterfield LH, Piesche M, Manos MP, Eastman LM, Dranoff G, Freeman GJ, Hodi FS. Soluble PD-L1 as a Biomarker in Malignant Melanoma Treated with Checkpoint Blockade. Cancer Immunol Res. 2017 Jun;5(6):480-492.
    View on PubMed
  9. Boyiadzis M, Agha M, Redner RL, Sehgal A, Im A, Hou JZ, Farah R, Dorritie KA, Raptis A, Lim SH, Wang H, Lapteva N, Mei Z, Butterfield LH, Rooney CM, Whiteside TL. Phase 1 clinical trial of adoptive immunotherapy using "off-the-shelf" activated natural killer cells in patients with refractory and relapsed acute myeloid leukemia. Cytotherapy. 2017 Oct;19(10):1225-1232.
    View on PubMed
  10. Tawbi HA, Burgess M, Bolejack V, Van Tine BA, Schuetze SM, Hu J, D'Angelo S, Attia S, Riedel RF, Priebat DA, Movva S, Davis LE, Okuno SH, Reed DR, Crowley J, Butterfield LH, Salazar R, Rodriguez-Canales J, Lazar AJ, Wistuba II, Baker LH, Maki RG, Reinke D, Patel S. Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial. Lancet Oncol. 2017 Nov;18(11):1493-1501.
    View on PubMed
  11. Zahorchak AF, Macedo C, Hamm DE, Butterfield LH, Metes DM, Thomson AW. High PD-L1/CD86 MFI ratio and IL-10 secretion characterize human regulatory dendritic cells generated for clinical testing in organ transplantation. Cell Immunol. 2018 Jan;323:9-18.
    View on PubMed
  12. Müller S, Agnihotri S, Shoger KE, Myers MI, Smith N, Chaparala S, Villanueva CR, Chattopadhyay A, Lee AV, Butterfield LH, Diaz A, Okada H, Pollack IF, Kohanbash G. Peptide vaccine immunotherapy biomarkers and response patterns in pediatric gliomas. JCI Insight. 2018 Apr 5;3(7):e98791.
    View on PubMed
  13. Li C, Song B, Santos PM, Butterfield LH. Hepatocellular cancer-derived alpha fetoprotein uptake reduces CD1 molecules on monocyte-derived dendritic cells. Cell Immunol. 2019 Jan;335:59-67.
    View on PubMed
  14. Vujanovic L, Chuckran C, Lin Y, Ding F, Sander CA, Santos PM, Lohr J, Mashadi-Hossein A, Warren S, White A, Huang A, Kirkwood JM, Butterfield LH. CD56dim CD16- Natural Killer Cell Profiling in Melanoma Patients Receiving a Cancer Vaccine and Interferon-α. Front Immunol. 2019 Jan 29;10:14.
    View on PubMed
  15. Santos PM, Menk AV, Shi J, Tsung A, Delgoffe GM, Butterfield LH. Tumor-Derived α-Fetoprotein Suppresses Fatty Acid Metabolism and Oxidative Phosphorylation in Dendritic Cells. Cancer Immunol Res. 2019 Jun;7(6):1001-1012.
    View on PubMed
  16. Butterfield LH, Vujanovic L, Santos PM, Maurer DM, Gambotto A, Lohr J, Li C, Waldman J, Chandran U, Lin Y, Lin H, Tawbi HA, Tarhini AA, Kirkwood JM. Multiple antigen-engineered DC vaccines with or without IFNα to promote antitumor immunity in melanoma. J Immunother Cancer. 2019 Apr 24;7(1):113.
    View on PubMed
  17. Helmink BA, Reddy SM, Gao J, Zhang S, Basar R, Thakur R, Yizhak K, Sade-Feldman M, Blando J, Han G, Gopalakrishnan V, Xi Y, Zhao H, Amaria RN, Tawbi HA, Cogdill AP, Liu W, LeBleu VS, Kugeratski FG, Patel S, Davies MA, Hwu P, Lee JE, Gershenwald JE, Lucci A, Arora R, Woodman S, Keung EZ, Gaudreau PO, Reuben A, Spencer CN, Burton EM, Haydu LE, Lazar AJ, Zapassodi R, Hudgens CW, Ledesma DA, Ong S, Bailey M, Warren S, Rao D, Krijgsman O, Rozeman EA, Peeper D, Blank CU, Schumacher TN, Butterfield LH, Zelazowska MA, McBride KM, Kalluri R, Allison J, Petitprez F, Fridman WH, Sautes-Fridman C, Hacohen N, Rezvani K, Sharma P, Tetzlaff MT, Wang L, Wargo JA. B cells and tertiary lymphoid structures promote immunotherapy response. Nature. 2020 Jan;577(7791):549-555.
    View on PubMed
  18. Santos PM, Adamik J, Howes TR, Du S, Vujanovic L, Warren S, Gambotto A, Kirkwood JM, Butterfield LH. Impact of checkpoint blockade on cancer vaccine-activated CD8+ T cell responses. J Exp Med. 2020 Jul 6;217(7):e20191369.
    View on PubMed
  19. Mueller S, Taitt JM, Villanueva-Meyer JE, Bonner ER, Nejo T, Lulla RR, Goldman S, Banerjee A, Chi SN, Whipple NS, Crawford JR, Gauvain K, Nazemi KJ, Watchmaker PB, Almeida ND, Okada K, Salazar AM, Gilbert RD, Nazarian J, Molinaro AM, Butterfield LH, Prados MD, Okada H. Mass cytometry detects H3.3K27M-specific vaccine responses in diffuse midline glioma. J Clin Invest. 2020 Aug 20:140378.
    View on PubMed
  20. Maurer, DM, Adamik, J, Santos, PM, Shi, J, Shurin, MR, Kirkwood, JM, Storkus, WJ, and Butterfield, LH. Dysregulated NFkB-dependent ICOSL Expression in Human Dendritic Cell Vaccines Impairs T Cell Responses in Melanoma Patients. Cancer Immunol. Res. 2020, in press.

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