Clinical and immunophenotype correlating with response to immunotherapy in paediatric patients with primary liver carcinoma. A case series

Allison F. O'Neill; Alanna J. Church; Angela Feraco; Jennifer Spidle; Catherine B. Wall; Heung Bae Kim; Scott Elisofon; Khashayar Vakili; Max Pimkin; Neekesh V. Dharia; Nathan R. Shelman; Antonio R. Perez-Atayde; Carlos Rodriguez-Galindo

doi:10.1016/j.ebiom.2024.105147

Clinical and immunophenotype correlating with response to immunotherapy in paediatric patients with primary liver carcinoma. A case series

Allison F. O'Neill, Alanna J. Church, Angela Feraco, Jennifer Spidle, Catherine B. Wall, Heung Bae Kim, Scott Elisofon, Khashayar Vakili, Max Pimkin, Neekesh V. Dharia, Nathan R. Shelman, Antonio R. Perez-Atayde, Carlos Rodriguez-Galindo

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

Background: Paediatric hepatocellular carcinomas (HCC) traditionally arise in the context of a normal structural and functional liver and carry a dismal prognosis. While chemotherapy is the frontline standard, there is emerging interest in the study of immunotherapies for paediatric patients with relapsed/refractory disease. There is limited data to support whether immunotherapies will be of utility in this patient population. Methods: Six paediatric patients (median age:16 years, range: 12–17 at the time of treatment) with advanced hepatocellular neosplams, either conventional hepatocellular or fibrolamellar carcinoma, were treated with immunotherapy. Patients were consented to institutional genomic profiling and biobanking protocols. Baseline samples and serial tissue samples, when available, were evaluated for somatic mutation rate, actionable gene mutations, and pan-immune bulk RNA expression profiling. Results were correlated with clinical course. Findings: Three patients responded to checkpoint inhibition: one achieved a complete, durable response and the other two, prolonged stable disease. Three additional patients progressed. Diagnostic tissue from the complete responder demonstrated a higher relative mutational burden and robust immune infiltrate. Pre-treatment samples from the three responders demonstrated decreased expression of genes associated with T-cell dysfunction. Interpretation: A subset of patients with primary paediatric hepatocellular tumours will respond to immunotherapy. Immunotherapies are currently under prospective study for relapsed/refractory liver tumours in paediatric patients. Results from this report support the prospective collection of serial serum and tissue samples which may further identify genomic and immunophenotypic patterns predictive of response. Funding: This work was supported by Philanthropic funds (Pan Mass Challenge, Team Angus and Team Perspective).

Original language	English
Article number	105147
Journal	EBioMedicine
Volume	104
DOIs	https://doi.org/10.1016/j.ebiom.2024.105147
State	Published - Jun 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors

Funding

All authors report no conflicts of interest relevant to this article. A.C. has received grants or contracts from the Children’s Oncology Group, the National Cancer Institute and the American Academy of Cancer Research; she is likewise a consultant for Jackson Laboratories and has received speaker fees from Tecan. N.V.D. and M.P were former employees of Dana-Farber Cancer Institute when the patients described were cared for; N.V.D is now an employee of Genentech, a member of the Roche Group where he has a patent pending. N.V.D. was receiving funding from Julia’s Legacy of Hope Street and the Baldrick’s Foundation Fellowship, unrelated to this work, but during the time period during which this work was being performed. M.P. is now an employee of Takeda. K.V. has a patent pending for a liver cancer therapeutic agent and stock options with ZEsST Bio.

Funders	Funder number
St. Baldrick’s Foundation

Keywords

Genomics
Hepatocellular carcinoma
Immunophenotype
Pediatric

ASJC Scopus subject areas

General Medicine
General Biochemistry, Genetics and Molecular Biology

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Cite this

O'Neill, A. F., Church, A. J., Feraco, A., Spidle, J., Wall, C. B., Kim, H. B., Elisofon, S., Vakili, K., Pimkin, M., Dharia, N. V., Shelman, N. R., Perez-Atayde, A. R., & Rodriguez-Galindo, C. (2024). Clinical and immunophenotype correlating with response to immunotherapy in paediatric patients with primary liver carcinoma. A case series. EBioMedicine, 104, Article 105147. https://doi.org/10.1016/j.ebiom.2024.105147

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title = "Clinical and immunophenotype correlating with response to immunotherapy in paediatric patients with primary liver carcinoma. A case series",

abstract = "Background: Paediatric hepatocellular carcinomas (HCC) traditionally arise in the context of a normal structural and functional liver and carry a dismal prognosis. While chemotherapy is the frontline standard, there is emerging interest in the study of immunotherapies for paediatric patients with relapsed/refractory disease. There is limited data to support whether immunotherapies will be of utility in this patient population. Methods: Six paediatric patients (median age:16 years, range: 12–17 at the time of treatment) with advanced hepatocellular neosplams, either conventional hepatocellular or fibrolamellar carcinoma, were treated with immunotherapy. Patients were consented to institutional genomic profiling and biobanking protocols. Baseline samples and serial tissue samples, when available, were evaluated for somatic mutation rate, actionable gene mutations, and pan-immune bulk RNA expression profiling. Results were correlated with clinical course. Findings: Three patients responded to checkpoint inhibition: one achieved a complete, durable response and the other two, prolonged stable disease. Three additional patients progressed. Diagnostic tissue from the complete responder demonstrated a higher relative mutational burden and robust immune infiltrate. Pre-treatment samples from the three responders demonstrated decreased expression of genes associated with T-cell dysfunction. Interpretation: A subset of patients with primary paediatric hepatocellular tumours will respond to immunotherapy. Immunotherapies are currently under prospective study for relapsed/refractory liver tumours in paediatric patients. Results from this report support the prospective collection of serial serum and tissue samples which may further identify genomic and immunophenotypic patterns predictive of response. Funding: This work was supported by Philanthropic funds (Pan Mass Challenge, Team Angus and Team Perspective).",

keywords = "Genomics, Hepatocellular carcinoma, Immunophenotype, Pediatric",

author = "O'Neill, \{Allison F.\} and Church, \{Alanna J.\} and Angela Feraco and Jennifer Spidle and Wall, \{Catherine B.\} and Kim, \{Heung Bae\} and Scott Elisofon and Khashayar Vakili and Max Pimkin and Dharia, \{Neekesh V.\} and Shelman, \{Nathan R.\} and Perez-Atayde, \{Antonio R.\} and Carlos Rodriguez-Galindo",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors",

year = "2024",

month = jun,

doi = "10.1016/j.ebiom.2024.105147",

language = "English",

volume = "104",

}

O'Neill, AF, Church, AJ, Feraco, A, Spidle, J, Wall, CB, Kim, HB, Elisofon, S, Vakili, K, Pimkin, M, Dharia, NV, Shelman, NR, Perez-Atayde, AR & Rodriguez-Galindo, C 2024, 'Clinical and immunophenotype correlating with response to immunotherapy in paediatric patients with primary liver carcinoma. A case series', EBioMedicine, vol. 104, 105147. https://doi.org/10.1016/j.ebiom.2024.105147

TY - JOUR

T1 - Clinical and immunophenotype correlating with response to immunotherapy in paediatric patients with primary liver carcinoma. A case series

AU - O'Neill, Allison F.

AU - Church, Alanna J.

AU - Feraco, Angela

AU - Spidle, Jennifer

AU - Wall, Catherine B.

AU - Kim, Heung Bae

AU - Elisofon, Scott

AU - Vakili, Khashayar

AU - Pimkin, Max

AU - Dharia, Neekesh V.

AU - Shelman, Nathan R.

AU - Perez-Atayde, Antonio R.

AU - Rodriguez-Galindo, Carlos

PY - 2024/6

Y1 - 2024/6

N2 - Background: Paediatric hepatocellular carcinomas (HCC) traditionally arise in the context of a normal structural and functional liver and carry a dismal prognosis. While chemotherapy is the frontline standard, there is emerging interest in the study of immunotherapies for paediatric patients with relapsed/refractory disease. There is limited data to support whether immunotherapies will be of utility in this patient population. Methods: Six paediatric patients (median age:16 years, range: 12–17 at the time of treatment) with advanced hepatocellular neosplams, either conventional hepatocellular or fibrolamellar carcinoma, were treated with immunotherapy. Patients were consented to institutional genomic profiling and biobanking protocols. Baseline samples and serial tissue samples, when available, were evaluated for somatic mutation rate, actionable gene mutations, and pan-immune bulk RNA expression profiling. Results were correlated with clinical course. Findings: Three patients responded to checkpoint inhibition: one achieved a complete, durable response and the other two, prolonged stable disease. Three additional patients progressed. Diagnostic tissue from the complete responder demonstrated a higher relative mutational burden and robust immune infiltrate. Pre-treatment samples from the three responders demonstrated decreased expression of genes associated with T-cell dysfunction. Interpretation: A subset of patients with primary paediatric hepatocellular tumours will respond to immunotherapy. Immunotherapies are currently under prospective study for relapsed/refractory liver tumours in paediatric patients. Results from this report support the prospective collection of serial serum and tissue samples which may further identify genomic and immunophenotypic patterns predictive of response. Funding: This work was supported by Philanthropic funds (Pan Mass Challenge, Team Angus and Team Perspective).

AB - Background: Paediatric hepatocellular carcinomas (HCC) traditionally arise in the context of a normal structural and functional liver and carry a dismal prognosis. While chemotherapy is the frontline standard, there is emerging interest in the study of immunotherapies for paediatric patients with relapsed/refractory disease. There is limited data to support whether immunotherapies will be of utility in this patient population. Methods: Six paediatric patients (median age:16 years, range: 12–17 at the time of treatment) with advanced hepatocellular neosplams, either conventional hepatocellular or fibrolamellar carcinoma, were treated with immunotherapy. Patients were consented to institutional genomic profiling and biobanking protocols. Baseline samples and serial tissue samples, when available, were evaluated for somatic mutation rate, actionable gene mutations, and pan-immune bulk RNA expression profiling. Results were correlated with clinical course. Findings: Three patients responded to checkpoint inhibition: one achieved a complete, durable response and the other two, prolonged stable disease. Three additional patients progressed. Diagnostic tissue from the complete responder demonstrated a higher relative mutational burden and robust immune infiltrate. Pre-treatment samples from the three responders demonstrated decreased expression of genes associated with T-cell dysfunction. Interpretation: A subset of patients with primary paediatric hepatocellular tumours will respond to immunotherapy. Immunotherapies are currently under prospective study for relapsed/refractory liver tumours in paediatric patients. Results from this report support the prospective collection of serial serum and tissue samples which may further identify genomic and immunophenotypic patterns predictive of response. Funding: This work was supported by Philanthropic funds (Pan Mass Challenge, Team Angus and Team Perspective).

KW - Genomics

KW - Hepatocellular carcinoma

KW - Immunophenotype

KW - Pediatric

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U2 - 10.1016/j.ebiom.2024.105147

DO - 10.1016/j.ebiom.2024.105147

M3 - Article

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AN - SCOPUS:85192831016

VL - 104

JO - EBioMedicine

JF - EBioMedicine

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ER -

Clinical and immunophenotype correlating with response to immunotherapy in paediatric patients with primary liver carcinoma. A case series

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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