Integrated immunological analysis of a successful conversion of locally advanced hepatocellular carcinoma to resectability with neoadjuvant therapy.

Journal for Immunotherapy of Cancer
Won Jin HoMark Yarchoan

Abstract

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer death worldwide with a minority of patients being diagnosed early enough for curative-intent interventions. We report the first use of preoperative cabozantinib plus nivolumab to successfully downstage what presented as unresectable HCC as part of an ongoing phase 1b study. Preoperative treatment with cabozantinib and nivolumab led to >99% reduction in alpha-fetoprotein, -37.3% radiographic reduction by RECIST 1.1 and a near complete pathologic response (80% to 100% necrosis). An integrated immunological analysis was performed on the post-treatment surgical tumor sample and matched pre-treatment and post-treatment peripheral blood samples with high-dimensional imaging and cytometry techniques. Bayesian non-negative matrix factorization (CoGAPS, Coordinated Gene Activity in Pattern Sets) and self-organizing map (FlowSOM) algorithms were used to distinguish changes in functional markers across cellular neighborhoods in the single cell data sets. Brisk immunological infiltration into the tumor microenvironment was observed in non-random, organized cellular neighborhoods. Systemically, combination therapy led to marked promotion of effector cytotoxic T cells and e...Continue Reading

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Citations

Jun 10, 2021·Expert Opinion on Investigational Drugs·D Brock HewittTimothy M Pawlik
Jul 31, 2021·Cancer Cell·Emily F Davis-MarcisakLuciane T Kagohara

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Methods Mentioned

BETA
surgical resection
biopsy

Clinical Trials Mentioned

NCT03299946

Software Mentioned

CoGAPS
histoCAT
CyTOF
FlowSOM

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