T Cell Lineage Imbalance and Regulatory Immune Populations in HCC Patients Undergoing Downstaging While Waitlisted for Liver Transplantation
1Institute of Translational Research, Ochsner Health System, New Orleans, LA
2Interventional Radiology, Ochsner Health System, New Orleans, LA
3Stanley S Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA.
Meeting: 2018 American Transplant Congress
Abstract number: B267
Keywords: Hepatocellular carcinoma, T cells, Tolerance
Session Information
Date: Sunday, June 3, 2018
Session Name: Poster Session B: Liver: Hepatocellular Carcinoma and Other Malignancies
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.« Back to 2018 American Transplant Congress