The focus of our lab is to develop and test new immune based approaches to treat cancer. Treatments that harness the immune system to fight cancer are revolutionizing the care of adult and pediatric cancer patients. The Dhodapkar lab is particularly interested in a type of immune therapy known as immune checkpoint blockade. We were involved in some of earliest studies applying such therapy in cancer and we are currently trying to understand how these therapies work. For example, why do some patients respond and others do not, and what are the mechanisms underlying adverse effects following these therapies? We use several high-content techniques, including novel single cell technologies to directly study patients receiving these therapies. The goals of our studies are to improve our current therapies by increasing responses and decreasing adverse effects.
In addition, we are also actively involved in studying the nature of naturally occurring immune responses in children with cancer and particularly how the immune system can alter the biology of these tumors. These studies are also expected to lead to discovery of new targets to manipulate the immune system in patients and harness the immune system to treat cancer in children. Immune-based strategies such as chimeric antigen receptor (CAR)-T cells are already showing promise for therapy of some childhood cancers. However, improved understanding of the biology of immune response will be essential to improving these therapies towards more durable responses.
Areas of Interest:
- Cell therapy
Hope Robinson, PhD, Postdoctoral Fellow
Julie Gilbert, MD, Fellow, Pediatric Hematology/Oncology
Alyssa Duffy, Graduate Student, Cancer Biology Program
Sayalee Potdar, Graduate Student, Cancer Biology Program
Renee Julia Manalo, Research Specialist
Kini Bailur JK, McCachren SS, Pendleton K, Vasquez J, Lim HS, Duffy A, Doxie DB, Kaushal A, Foster C, DeRyckere, Castellino S, Kemp ML, Dhodapkar MV, Dhodapkar KM. Risk associated alterations in marrow T cells in pediatric leukemia. JCI Insight. 2020. PMID: 32692727.
Robinson MH, Vasquez JC, Kaushal A, MacDonald TJ, Velazquez Vega J, Schniederjan M, Dhodapkar KM. Subtype and Grade-dependent Spatial Heterogeneity of T cell infiltration in Pediatric Glioma. J Immunother Cancer. 2020. PMID: 32788236.
Bar N, Costa F, Das R, Samur M, Gettinger SN, Neparidze N, Parker TL, Kini Bailur, J Pendleton K, Bajpai R, Zhang L, Xu ML, Anderson T, Giuliani N, Shanmugam M, Dhodapkar KM, Dhodapkar MV. Myeloid inflammation is differentially affected by PD-L1 versus PD-1 blockade therapy. JCI Insight. 2020 May 19:129353.doi: 10.1172/jci.insight.129353. PMID: 32427579.
Das R, Bar N, Ferreira M, Newman AM, Zhang L, Bailur JK, Bacchiocchi A, Kluger H, Wei W, Halaban R, Sznol M, Dhodapkar MV, Dhodapkar KM. Early B cell changes predict autoimmunity following combination immune checkpoint blockade. J Clin Invest. 2018 Feb 1;128(2):715-720. doi: 10.1172/JCI96798. Epub 2018 Jan 8. PMID: 29309048.
Boddupalli S, Bar N, Kadaveru K, Krauthammer M, Pornputtapong N, Mai Z, Ariyan S, Narayan D, Kluger H, Deng Y, Verma R, Das R, Bacchiocchi A, Halaban R, Sznol M, Dhodapkar MV, Dhodapkar KM. Inter-lesional diversity of T-cell receptors in melanoma with immune-checkpoints enriched in tissue-resident memory T cells. JCI Insight. 2016 Dec 22;1(21):e88955. doi: 10.1172/jci.insight.88955. PMID: 28018970.
Das R, Verma R, Sznol M, Boddupalli S, Bacchiocchi A, Gettinger S, Kluger H, Callahan M, Wolchok J, Halaban R, Dhodapkar M, Dhodapkar KM. Combination therapy with anti-CTLA4 and anti-PD1 leads to distinct immunologic changes in-vivo. J Immunol. 2015 Feb 1;194(3):950-9. PMID: 32788236.
Sehgal K, Guo X, Kodoru S, Lin A and Dhodapkar KM. Cross-talk between interferon signaling and FcR in the pathogenesis and therapeutic response of children with immune thrombocytopenia: role for both plasmacytoid dendritic cells and myeloid cells. Science Translational Medicine. 2013 Jul 10;5(193):193ra89. PMID: 23843450.
NIH R01 AR077926-01 – 08/15/2020-06/30/2024
Title: B cell depletion to prevent autoimmunity
NIH 1R56 AI145231-01 – 07/01/2020-03/31/2024
Using donor dendritic cells to optimize GvHD and GvL in allogeneic stem cell transplantation
PI: E. Waller
NIH R21 CA238108-01A1 – 07/01/2020-06/30/2022
Anti-SOX2 Immunotherapy to prevent multiple myeloma relapse
Role: Co-I (Emory Site PI)
NIH:1R01CA238471-01 – 4/1/2019-3/31/2024
B cells in autoimmunity following checkpoint blockade
NIH K12 5K12CA237806-02 – 07/02/2019-06/30/2024
Emory Clinical Oncology Career Development Award
Private Foundation Funding:
Winship Invest$ Pilot Grant
Clinical trial of Rituxan to prevent autoimmunity following combination checkpoint blockade
Specialized Center of Research Program – Leukemia Lymphoma Society – 1/2020-12/2024
Improving targeted adoptive cell therapy of myeloma
Peach Bowl LegACy Fund – 2/1/2020-1/31/2022
Phase I study of WP1066 in children with refractory and progressive or recurrent malignant brain tumors