Tags

Type your tag names separated by a space and hit enter

Unique T-Cell Populations Define Immune-Inflamed Hepatocellular Carcinoma.

Abstract

BACKGROUND & AIMS

The characterization of T cells infiltrating hepatocellular carcinoma (HCC) provides information on cancer immunity and also on selection of patients with precise indication of immunotherapy. The aim of the study was to characterize T-cell populations within tumor tissue and compare them with non-neoplastic liver tissue as well as circulating cells of the same patients.

METHODS

The presence of unique cell populations was investigated in 36 HCC patients by multidimensional flow cytometry followed by t-distributed stochastic neighbor embedding analysis. Functional activity of tumor-infiltrating T cells was determined after activation by phorbol 12-myristate 13-acetate and ionomycin.

RESULTS

Within the tumor there were more cells expressing CD137 and ICOS than in non-neoplastic liver tissue, possibly after recent antigenic activation. These cells contained several populations, including the following: (1) functionally impaired, proliferating CD4+ cells co-expressing ICOS and TIGIT; (2) functionally active CD8+ cells co-expressing CD38 and PD1; and (3) CD4-CD8 double-negative T-cell receptor αβ and γδ cells (both non-major histocompatibility complex-restricted T cells). When the identified clusters were compared with histologic classification performed on the same samples, an accumulation of activated T cells was observed in immune-inflamed HCC. The same analyses performed in 7 patients receiving nivolumab treatment showed a remarkable reduction in the functionally impaired CD4+ cells, which returned to almost normal activity over time.

CONCLUSIONS

Unique populations of activated T cells are present in HCC tissue, whose antigen specificity remains to be investigated. Some of these cell populations are functionally impaired and nivolumab treatment restores their responsiveness. The finding of ongoing immune response within the tumor shows which lymphocyte populations are impaired within the HCC and identifies the patients who might take benefit from immunotherapy.

Authors+Show Affiliations

Experimental Immunology, Department of Biomedicine, University of Basel, Switzerland; Hepatology Laboratory, Department of Biomedicine, University of Basel, Switzerland.Hepatology Laboratory, Department of Biomedicine, University of Basel, Switzerland; Division of Gastroenterology and Hepatology, University Hospital Basel, Basel, Switzerland.Experimental Immunology, Department of Biomedicine, University of Basel, Switzerland.Institute of Pathology, Division of Molecular Pathology, University Hospital Basel, Basel, Switzerland.Hepatology Laboratory, Department of Biomedicine, University of Basel, Switzerland; Division of Gastroenterology and Hepatology, University Hospital Basel, Basel, Switzerland. Electronic address: markus.heim@unibas.ch.Experimental Immunology, Department of Biomedicine, University of Basel, Switzerland. Electronic address: gennaro.delibero@unibas.ch.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31445190

Citation

Di Blasi, Daniela, et al. "Unique T-Cell Populations Define Immune-Inflamed Hepatocellular Carcinoma." Cellular and Molecular Gastroenterology and Hepatology, 2019.
Di Blasi D, Boldanova T, Mori L, et al. Unique T-Cell Populations Define Immune-Inflamed Hepatocellular Carcinoma. Cell Mol Gastroenterol Hepatol. 2019.
Di Blasi, D., Boldanova, T., Mori, L., Terracciano, L., Heim, M. H., & De Libero, G. (2019). Unique T-Cell Populations Define Immune-Inflamed Hepatocellular Carcinoma. Cellular and Molecular Gastroenterology and Hepatology, doi:10.1016/j.jcmgh.2019.08.004.
Di Blasi D, et al. Unique T-Cell Populations Define Immune-Inflamed Hepatocellular Carcinoma. Cell Mol Gastroenterol Hepatol. 2019 Aug 22; PubMed PMID: 31445190.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Unique T-Cell Populations Define Immune-Inflamed Hepatocellular Carcinoma. AU - Di Blasi,Daniela, AU - Boldanova,Tujana, AU - Mori,Lucia, AU - Terracciano,Luigi, AU - Heim,Markus H, AU - De Libero,Gennaro, Y1 - 2019/08/22/ PY - 2019/02/26/received PY - 2019/08/08/revised PY - 2019/08/09/accepted PY - 2019/8/25/pubmed PY - 2019/8/25/medline PY - 2019/8/25/entrez KW - Cancer Immunity KW - Immunotherapy KW - tSNE Analysis JF - Cellular and molecular gastroenterology and hepatology JO - Cell Mol Gastroenterol Hepatol N2 - BACKGROUND & AIMS: The characterization of T cells infiltrating hepatocellular carcinoma (HCC) provides information on cancer immunity and also on selection of patients with precise indication of immunotherapy. The aim of the study was to characterize T-cell populations within tumor tissue and compare them with non-neoplastic liver tissue as well as circulating cells of the same patients. METHODS: The presence of unique cell populations was investigated in 36 HCC patients by multidimensional flow cytometry followed by t-distributed stochastic neighbor embedding analysis. Functional activity of tumor-infiltrating T cells was determined after activation by phorbol 12-myristate 13-acetate and ionomycin. RESULTS: Within the tumor there were more cells expressing CD137 and ICOS than in non-neoplastic liver tissue, possibly after recent antigenic activation. These cells contained several populations, including the following: (1) functionally impaired, proliferating CD4+ cells co-expressing ICOS and TIGIT; (2) functionally active CD8+ cells co-expressing CD38 and PD1; and (3) CD4-CD8 double-negative T-cell receptor αβ and γδ cells (both non-major histocompatibility complex-restricted T cells). When the identified clusters were compared with histologic classification performed on the same samples, an accumulation of activated T cells was observed in immune-inflamed HCC. The same analyses performed in 7 patients receiving nivolumab treatment showed a remarkable reduction in the functionally impaired CD4+ cells, which returned to almost normal activity over time. CONCLUSIONS: Unique populations of activated T cells are present in HCC tissue, whose antigen specificity remains to be investigated. Some of these cell populations are functionally impaired and nivolumab treatment restores their responsiveness. The finding of ongoing immune response within the tumor shows which lymphocyte populations are impaired within the HCC and identifies the patients who might take benefit from immunotherapy. SN - 2352-345X UR - https://www.unboundmedicine.com/medline/citation/31445190/Unique_T_cell_populations_define_immune-inflamed_Hepatocellular_Carcinoma L2 - https://linkinghub.elsevier.com/retrieve/pii/S2352-345X(19)30110-9 DB - PRIME DP - Unbound Medicine ER -