Multiple immune-suppressive mechanisms in fibrolamellar carcinoma

Amy K. Kim, Faiz Gani, Andrew J. Layman, Sepideh Besharati, Qingfeng Zhu, Farah Succaria, Elizabeth L. Engle, Feriyl Bhaijee, Maria B. Goggins, Nicolas J. Llosa, Timothy M. Pawlik, Mark Yarchoan, Elizabeth M. Jaffee, Howard C. Simons, Janis M. Taube, Robert A. Anders

Research output: Contribution to journalArticlepeer-review

Abstract

Fibrolamellar carcinoma (FLC) is a rare type of liver cancer that affects adolescents and young adults. The most effective treatment for FLC is surgical resection, but no standardized systemic therapy exists for patients with recurrent or unresectable FLC. As a first step to understand the immune microenvironment of FLC, we investigated targetable immune-checkpoint pathways, PD-1, PD-L1, B7-H3, IDO-1, and LAG3, in relation to CD8þ cytotoxic T-lymphocyte density. Thirty-two FLC tumor specimens were analyzed using IHC staining for PD-L1, CD8, PD-1, IDO, LAG3, and B7-H3. Sixty-three percent of FLC cases demonstrated membranous PD-L1 expression on tumor cells, and almost 70% of cases demonstrated PD-L1þ tumor-infiltrating lymphocytes and tumor-associated macrophages (TIL/TAM). Myeloid-derived cells appeared to be a major component of PD-L1þ tumor-infiltrating immune cells. Forty percent of the cases showed B7-H3 expression in the tumor zone, with 91% cases showing B7-H3 expression in TILs and TAMs. IDO and PD-1 expression was highest in the tumor interface zone. B7-H3 or IDO expression on tumor cells significantly correlated with higher CD8þ T-cell density. In conclusion, a high proportion of FLC cases showed robust expression of PD-1, PD-L1, B7-H3, and IDO in an adaptive immune-resistance pattern. Our findings provide further basis for targeting these different immune-checkpoint axes in FLC.

Original languageEnglish (US)
Pages (from-to)805-812
Number of pages8
JournalCancer Immunology Research
Volume7
Issue number5
DOIs
StatePublished - May 2019

ASJC Scopus subject areas

  • Immunology
  • Cancer Research

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