Deep profiling of human hepatocellular carcinoma immune infiltrates: Involvement of CD103+ resident memory-like T and NK cells
Joe Yeong1,2, Harsimran Singh1, Yang Cheng1, Karen Teng1, Antonio Bertoletti1,3, Seng Gee Lim4, Tony Kiat Hon Lim2, Su Pin Choo5, Evan W. Newell1*
1Agency for Science, Technology and Research (A*STAR), Singapore Immunology Network (SIgN); 2Division of Pathology, Singapore General Hospital; 3Duke-NUS Medical School; 4National University Health System; 5Medical Oncology, National Cancer Centre Singapore
Although highly vascularized and infiltrated with a large number of lymphocytes, the liver is unique in its tolerogenic properties. Our lab is interested in understanding the peculiarities of liver-localized antigen-specific T cell mediated immune responses to both hepatitis B virus (HBV) and hepatocellular carcinoma (HCC). We report that tracking and profiling of HBV-specific T cell populations using mass cytometry and highly multiplexed peptide-MHC tetramer staining allows for identification of T cell correlates of chronic HBV infection status across various patient cohorts. In parallel, following up on our previous study (Wong et al., Immunity 2016) that identified and profiled CD69+CD103+ resident T and NK cell populations in liver samples obtained from healthy donors, we compared the features of these and other resident lymphocyte populations derived from adjacent normal vs. tumor of HCC patients. Consistent with observations from other tumors, but not necessarily expected for liver, we found that resident memory-like T and intraepithelial ILC1 (ieILC1)-like NK cells are variably enriched in HCC tumors with elevated expression of activation markers such as Ki67, CD38 and PD-1, indicating their possible involvement in the anti-tumoral response and patient prognosis. The in situ localizations of these cells were also assessed using multiplexed fluorescent immunohistochemistry. Ongoing studies aim to compare the characteristics of HBV and HCC specific T cells derived from blood and liver tissues of HBV and HBV-related HCC patient samples to identify T cell based biomarkers for a variety of clinical outcomes.
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