Approaches to Spatially Resolving the Tumour Immune Microenvironment of Hepatocellular Carcinoma

Overview

Journal Ther Adv Med Oncol

Specialty Oncology

Date 2022 Jul 28

PMID 35898965

Authors

Felix Marsh-Wakefield

Angela L Ferguson

Ken Liu

Cositha Santhakumar

Geoffrey McCaughan

Umaimainthan Palendira

Affiliations

Soon will be listed here.

Abstract

Hepatocellular carcinoma (HCC) is a common and deadly cancer worldwide. Many factors contribute to mortality and place an individual at high risk of developing HCC, including viral infection, alcohol intake, metabolic-associated disease, autoimmunity and genetic liver disorders. Although there are many therapeutics available, much about this disease remains to be understood. This is most evident when investigating the tumour microenvironment (TME). Both innate and adaptive immune cells have been associated with carcinogenesis within the TME of HCC patients. The ability to interrogate the TME more thoroughly with spatial technologies continues to improve, both at the experimental and analytical stages. This review provides insight into technologies available to investigate the TME, and how such technologies are beneficial for improving our understanding of HCC carcinogenesis.

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References

Fang J, Xu L, Shang L, Pan C, Ding J, Tang Y . Vessels That Encapsulate Tumor Clusters (VETC) Pattern Is a Predictor of Sorafenib Benefit in Patients with Hepatocellular Carcinoma. Hepatology. 2018; 70(3):824-839. DOI: 10.1002/hep.30366. View

Wallace M, Preen D, Short M, Adams L, Jeffrey G . Hepatocellular carcinoma in Australia 1982-2014: Increasing incidence and improving survival. Liver Int. 2018; 39(3):522-530. DOI: 10.1111/liv.13966. View

Fessas P, Spina P, Boldorini R, Pirisi M, Minisini R, Mauri F . Phenotypic Characteristics of the Tumour Microenvironment in Primary and Secondary Hepatocellular Carcinoma. Cancers (Basel). 2021; 13(9). PMC: 8124398. DOI: 10.3390/cancers13092137. View

Heinrich B, Gertz E, Schaffer A, Craig A, Ruf B, Subramanyam V . The tumour microenvironment shapes innate lymphoid cells in patients with hepatocellular carcinoma. Gut. 2021; 71(6):1161-1175. PMC: 8807808. DOI: 10.1136/gutjnl-2021-325288. View

Llovet J, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc J . Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008; 359(4):378-90. DOI: 10.1056/NEJMoa0708857. View

Dong P, Ma L, Liu L, Zhao G, Zhang S, Dong L . CD86⁺/CD206⁺, Diametrically Polarized Tumor-Associated Macrophages, Predict Hepatocellular Carcinoma Patient Prognosis. Int J Mol Sci. 2016; 17(3):320. PMC: 4813183. DOI: 10.3390/ijms17030320. View

Fang J, Zhou H, Zhang C, Shang L, Zhang L, Xu J . A novel vascular pattern promotes metastasis of hepatocellular carcinoma in an epithelial-mesenchymal transition-independent manner. Hepatology. 2015; 62(2):452-65. DOI: 10.1002/hep.27760. View

Faget L, Hnasko T . Tyramide Signal Amplification for Immunofluorescent Enhancement. Methods Mol Biol. 2015; 1318:161-72. DOI: 10.1007/978-1-4939-2742-5_16. View

Stahl P, Salmen F, Vickovic S, Lundmark A, Fernandez Navarro J, Magnusson J . Visualization and analysis of gene expression in tissue sections by spatial transcriptomics. Science. 2016; 353(6294):78-82. DOI: 10.1126/science.aaf2403. View

10.

Ashhurst T, Marsh-Wakefield F, Putri G, Spiteri A, Shinko D, Read M . Integration, exploration, and analysis of high-dimensional single-cell cytometry data using Spectre. Cytometry A. 2021; 101(3):237-253. DOI: 10.1002/cyto.a.24350. View

11.

Brunner S, Itzel T, Rubner C, Kesselring R, Griesshammer E, Evert M . Tumor-infiltrating B cells producing antitumor active immunoglobulins in resected HCC prolong patient survival. Oncotarget. 2017; 8(41):71002-71011. PMC: 5642613. DOI: 10.18632/oncotarget.20238. View

12.

Oura K, Morishita A, Tani J, Masaki T . Tumor Immune Microenvironment and Immunosuppressive Therapy in Hepatocellular Carcinoma: A Review. Int J Mol Sci. 2021; 22(11). PMC: 8198390. DOI: 10.3390/ijms22115801. View

13.

Phillips D, Schurch C, Khodadoust M, Kim Y, Nolan G, Jiang S . Highly Multiplexed Phenotyping of Immunoregulatory Proteins in the Tumor Microenvironment by CODEX Tissue Imaging. Front Immunol. 2021; 12:687673. PMC: 8170307. DOI: 10.3389/fimmu.2021.687673. View

14.

El-Khoueiry A, Sangro B, Yau T, Crocenzi T, Kudo M, Hsu C . Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet. 2017; 389(10088):2492-2502. PMC: 7539326. DOI: 10.1016/S0140-6736(17)31046-2. View

15.

Shalapour S, Lin X, Bastian I, Brain J, Burt A, Aksenov A . Erratum: Inflammation-induced IgA cells dismantle anti-liver cancer immunity. Nature. 2017; 552(7685):430. PMC: 8594569. DOI: 10.1038/nature25028. View

16.

Zhu A, Finn R, Edeline J, Cattan S, Ogasawara S, Palmer D . Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial. Lancet Oncol. 2018; 19(7):940-952. DOI: 10.1016/S1470-2045(18)30351-6. View

17.

Zhou S, Yin D, Hu Z, Luo C, Zhou Z, Xin H . A Positive Feedback Loop Between Cancer Stem-Like Cells and Tumor-Associated Neutrophils Controls Hepatocellular Carcinoma Progression. Hepatology. 2019; 70(4):1214-1230. DOI: 10.1002/hep.30630. View

18.

Komiyama S, Yamada T, Takemura N, Kokudo N, Hase K, Kawamura Y . Profiling of tumour-associated microbiota in human hepatocellular carcinoma. Sci Rep. 2021; 11(1):10589. PMC: 8134445. DOI: 10.1038/s41598-021-89963-1. View

19.

Sheng J, Zhang J, Wang L, Tano V, Tang J, Wang X . Topological analysis of hepatocellular carcinoma tumour microenvironment based on imaging mass cytometry reveals cellular neighbourhood regulated reversely by macrophages with different ontogeny. Gut. 2021; 71(6):1176-1191. DOI: 10.1136/gutjnl-2021-324339. View

20.

Han E, Lee Y, Liao W, Liu Y, Liao H, Jeng L . Direct tissue analysis by MALDI-TOF mass spectrometry in human hepatocellular carcinoma. Clin Chim Acta. 2010; 412(3-4):230-9. DOI: 10.1016/j.cca.2010.09.021. View