Impact of immune tolerance mechanisms on the efficacy of immunotherapy in primary and secondary liver cancers

Kamya Sankar; Ashley N Pearson; Tejaswi Worlikar; Matthew D Perricone; Erin A Holcomb; Mishal Mendiratta-Lala; Zhen Xu; Neil Bhowmick; Michael D Green

doi:10.21037/tgh-23-11

Impact of immune tolerance mechanisms on the efficacy of immunotherapy in primary and secondary liver cancers

Transl Gastroenterol Hepatol. 2023 Jun 27:8:29. doi: 10.21037/tgh-23-11. eCollection 2023.

Authors

Kamya Sankar¹, Ashley N Pearson^{2

3

4}, Tejaswi Worlikar⁵, Matthew D Perricone⁶, Erin A Holcomb^{2

3

4}, Mishal Mendiratta-Lala⁷, Zhen Xu⁵, Neil Bhowmick¹, Michael D Green^{2

3

4

8

9}

Affiliations

¹ Division of Medical Oncology, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
² Graduate Program in Immunology, School of Medicine, University of Michigan, Ann Arbor, MI, USA.
³ Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
⁴ Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
⁵ Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
⁶ Program in Biomedical Sciences, University of Michigan Medical School, Ann Arbor, MI, USA.
⁷ Department of Radiology, University of Michigan, Ann Arbor, MI, USA.
⁸ Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, USA.
⁹ Department of Radiation Oncology, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI, USA.

Abstract

The liver is a functionally unique organ with an immunosuppressive microenvironment. The liver is the sixth most common site of primary cancer in humans and is a frequent site of metastasis from other solid tumors. The development of effective therapies for primary and metastatic liver cancer has been challenging due to the complex metabolic and immune microenvironment of the liver. The liver tumor microenvironment (TME) in primary and secondary (metastatic) liver cancers is heterogenous and consists of unique immune and stromal cell populations. Crosstalk between these cell populations and tumor cells creates an immunosuppressive microenvironment within the liver which potentiates cancer progression. Immune checkpoint inhibitors (ICIs) are now clinically approved for the management of primary and secondary liver cancer and can partially overcome liver immune tolerance, but their efficacy is limited. In this review, we describe the liver microenvironment and the use of immunotherapy in primary and secondary liver cancer. We discuss emerging combination strategies utilizing locoregional and systemic therapy approaches which may enhance efficacy of immunotherapy in primary and secondary liver cancer. A deeper understanding of the immunosuppressive microenvironment of the liver will inform novel therapies and therapeutic combinations in order to improve outcomes of patients with primary and secondary liver cancer.

Keywords: Hepatocellular carcinoma (HCC); immunotherapy in liver cancer; liver metastases; tumor immune microenvironment.

Publication types

Review

Abstract

Publication types

Grants and funding