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Transarterial Embolization Modulates the Immune Response within Target and Nontarget Hepatocellular Carcinomas in a Rat Model.
Tischfield, David J; Gurevich, Alexey; Johnson, Omar; Gatmaytan, Isabela; Nadolski, Gregory J; Soulen, Michael C; Kaplan, David E; Furth, Emma; Hunt, Stephen J; Gade, Terence P F.
Afiliação
  • Tischfield DJ; From the Penn Image-Guided Interventions Laboratory (D.J.T., A.G., O.J., I.G., G.J.N., S.J.H., T.P.F.G.), Department of Radiology (D.J.T., O.J., G.J.N., M.C.S., S.J.H., T.P.F.G.), and Department of Pathology (E.F.), Hospital of the University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104;
  • Gurevich A; From the Penn Image-Guided Interventions Laboratory (D.J.T., A.G., O.J., I.G., G.J.N., S.J.H., T.P.F.G.), Department of Radiology (D.J.T., O.J., G.J.N., M.C.S., S.J.H., T.P.F.G.), and Department of Pathology (E.F.), Hospital of the University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104;
  • Johnson O; From the Penn Image-Guided Interventions Laboratory (D.J.T., A.G., O.J., I.G., G.J.N., S.J.H., T.P.F.G.), Department of Radiology (D.J.T., O.J., G.J.N., M.C.S., S.J.H., T.P.F.G.), and Department of Pathology (E.F.), Hospital of the University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104;
  • Gatmaytan I; From the Penn Image-Guided Interventions Laboratory (D.J.T., A.G., O.J., I.G., G.J.N., S.J.H., T.P.F.G.), Department of Radiology (D.J.T., O.J., G.J.N., M.C.S., S.J.H., T.P.F.G.), and Department of Pathology (E.F.), Hospital of the University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104;
  • Nadolski GJ; From the Penn Image-Guided Interventions Laboratory (D.J.T., A.G., O.J., I.G., G.J.N., S.J.H., T.P.F.G.), Department of Radiology (D.J.T., O.J., G.J.N., M.C.S., S.J.H., T.P.F.G.), and Department of Pathology (E.F.), Hospital of the University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104;
  • Soulen MC; From the Penn Image-Guided Interventions Laboratory (D.J.T., A.G., O.J., I.G., G.J.N., S.J.H., T.P.F.G.), Department of Radiology (D.J.T., O.J., G.J.N., M.C.S., S.J.H., T.P.F.G.), and Department of Pathology (E.F.), Hospital of the University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104;
  • Kaplan DE; From the Penn Image-Guided Interventions Laboratory (D.J.T., A.G., O.J., I.G., G.J.N., S.J.H., T.P.F.G.), Department of Radiology (D.J.T., O.J., G.J.N., M.C.S., S.J.H., T.P.F.G.), and Department of Pathology (E.F.), Hospital of the University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104;
  • Furth E; From the Penn Image-Guided Interventions Laboratory (D.J.T., A.G., O.J., I.G., G.J.N., S.J.H., T.P.F.G.), Department of Radiology (D.J.T., O.J., G.J.N., M.C.S., S.J.H., T.P.F.G.), and Department of Pathology (E.F.), Hospital of the University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104;
  • Hunt SJ; From the Penn Image-Guided Interventions Laboratory (D.J.T., A.G., O.J., I.G., G.J.N., S.J.H., T.P.F.G.), Department of Radiology (D.J.T., O.J., G.J.N., M.C.S., S.J.H., T.P.F.G.), and Department of Pathology (E.F.), Hospital of the University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104;
  • Gade TPF; From the Penn Image-Guided Interventions Laboratory (D.J.T., A.G., O.J., I.G., G.J.N., S.J.H., T.P.F.G.), Department of Radiology (D.J.T., O.J., G.J.N., M.C.S., S.J.H., T.P.F.G.), and Department of Pathology (E.F.), Hospital of the University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104;
Radiology ; 303(1): 215-225, 2022 04.
Article em En | MEDLINE | ID: mdl-35014906
ABSTRACT
Background Transarterial embolization (TAE) is the most common treatment for hepatocellular carcinoma (HCC); however, there remain limited data describing the influence of TAE on the tumor immune microenvironment. Purpose To characterize TAE-induced modulation of the tumor immune microenvironment in a rat model of HCC and identify factors that modulate this response. Materials and Methods TAE was performed on autochthonous HCCs induced in rats with use of diethylnitrosamine. CD3, CD4, CD8, and FOXP3 lymphocytes, as well as programmed cell death protein ligand-1 (PD-L1) expression, were examined in three cohorts tumors from rats that did not undergo embolization (control), embolized tumors (target), and nonembolized tumors from rats that had a different target tumor embolized (nontarget). Differences in immune cell recruitment associated with embolic agent type (tris-acryl gelatin microspheres [TAGM] vs hydrogel embolics) and vascular location were examined in rat and human tissues. A generalized estimating equation model and t, Mann-Whitney U, and χ2 tests were used to compare groups. Results Cirrhosis-induced alterations in CD8, CD4, and CD25/CD4 lymphocytes were partially normalized following TAE (CD8 38.4%, CD4 57.6%, and CD25/CD4 21.1% in embolized liver vs 47.7% [P = .02], 47.0% [P = .01], and 34.9% [P = .03], respectively, in cirrhotic liver [36.1%, 59.6%, and 4.6% in normal liver]). Embolized tumors had a greater number of CD3, CD4, and CD8 tumor-infiltrating lymphocytes relative to controls (191.4 cells/mm2 vs 106.7 cells/mm2 [P = .03]; 127.8 cells/mm2 vs 53.8 cells/mm2 [P < .001]; and 131.4 cells/mm2 vs 78.3 cells/mm2 [P = .01]) as well as a higher PD-L1 expression score (4.1 au vs 1.9 au [P < .001]). A greater number of CD3, CD4, and CD8 lymphocytes were found near TAGM versus hydrogel embolics (4.1 vs 2.0 [P = .003]; 3.7 vs 2.0 [P = .01]; and 2.2 vs 1.1 [P = .03], respectively). The number of lymphocytes adjacent to embolics differed based on vascular location (17.9 extravascular CD68+ peri-TAGM cells vs 7.0 intravascular [P < .001]; 6.4 extravascular CD68+ peri-hydrogel embolic cells vs 3.4 intravascular [P < .001]). Conclusion Transarterial embolization-induced dynamic alterations of the tumor immune microenvironment are influenced by underlying liver disease, embolic agent type, and vascular location. © RSNA, 2022 Online supplemental material is available for this article. See also the editorials by Kennedy et al and by White in this issue.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Hepatocelular / Neoplasias Hepáticas Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Hepatocelular / Neoplasias Hepáticas Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article