Date: Sunday, June 3, 2018
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall 4EF
Purpose:In this study, we monitored peripheral lymphocyte lineage and regulatory immune populations in HCC patients undergoing DEB-TACE as a bridge to liver transplantation.
Methods: Liver transplant candidate HCC patients undergoing DEB-TACE were prospectively enrolled. Blood was collected before DEB-TACE (100-300[micro]m LC Beads with 100mg doxorubicin). Peripheral blood mononuclear cells were isolated, stained with lymphocyte and myeloid-derived suppressor cell (MDSCs) antibodies, and then analyzed by flow cytometry. Tumor response to DEB-TACE was determined using mRECIST imaging criteria.
Results: Patient cohort (n=56) consisted of 75% Hepatitis C, 70% male, with average MELD at DEB-TACE of 11 points. Lymphopenia was associated with primary non-objective response (mRECIST of stable disease or disease progression) to DEB-TACE (p<0.05). Patients were then stratified based on lymphopenia status (absolute lymphocyte counts < 1.2k/mL). Pre-treatment analysis of T cell lineage revealed lymphopenic patients had elevated CD4:CD8 T cell ratios. Both regulatory immune populations of MDSCs (CD33+CD14+HLA-DRLO/-) and regulatory T cells (Tregs, CD127NEGCD4+CD25HI) were significantly elevated in lymphopenic patients (p<0.01 and p<0.001, respectively). This was accompanied by a significant decrease in CD8:Treg ratio in patients with non-objective responses to DEB-TACE (p<0.05). In transplanted patients (n=14), 5/6 lymphopenic patients had significant MDSC expansion with viable lesion at explant compared to 3/8 in patients with normal lymphocyte counts. Two of three patients with satellite lesions at explant had lymphopenia, MDSC and Treg expansion.
Conclusions: Assessment of lymphocyte lineage and regulatory immune cells (MDSCs and Tregs) in HCC patients may help identify treatment resistant lesions with anti-tumor tolerance. These patients may benefit from adjuvant immunotherapies prior to liver transplant to aid immune-recognition of tumors.
CITATION INFORMATION: Thevenot P., Nunez K., Sandow T., Gimenez J., Gonzalez-Rosario J., Patel M., Alfadhli A., Wyczechowska D., Cohen A. T Cell Lineage Imbalance and Regulatory Immune Populations in HCC Patients Undergoing Downstaging While Waitlisted for Liver Transplantation Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Thevenot P, Nunez K, Sandow T, Gimenez J, Gonzalez-Rosario J, Patel M, Alfadhli A, Wyczechowska D, Cohen A. T Cell Lineage Imbalance and Regulatory Immune Populations in HCC Patients Undergoing Downstaging While Waitlisted for Liver Transplantation [abstract]. https://atcmeetingabstracts.com/abstract/t-cell-lineage-imbalance-and-regulatory-immune-populations-in-hcc-patients-undergoing-downstaging-while-waitlisted-for-liver-transplantation/. Accessed March 1, 2021.
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