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Review
. 2023 Apr 14;12(8):1165.
doi: 10.3390/cells12081165.

Organoids as an Enabler of Precision Immuno-Oncology

Junzhe Zhao  1   2   3 , Antoinette Fong  3 , See Voon Seow  2 , Han Chong Toh  2
Affiliations
Review

Organoids as an Enabler of Precision Immuno-Oncology

Junzhe Zhao et al. Cells. .

Abstract

Since the dawn of the past century, landmark discoveries in cell-mediated immunity have led to a greater understanding of the innate and adaptive immune systems and revolutionised the treatment of countless diseases, including cancer. Today, precision immuno-oncology (I/O) involves not only targeting immune checkpoints that inhibit T-cell immunity but also harnessing immune cell therapies. The limited efficacy in some cancers results mainly from a complex tumour microenvironment (TME) that, in addition to adaptive immune cells, comprises innate myeloid and lymphoid cells, cancer-associated fibroblasts, and the tumour vasculature that contribute towards immune evasion. As the complexity of TME has called for more sophisticated human-based tumour models, organoids have allowed the dynamic study of spatiotemporal interactions between tumour cells and individual TME cell types. Here, we discuss how organoids can study the TME across cancers and how these features may improve precision I/O. We outline the approaches to preserve or recapitulate the TME in tumour organoids and discuss their potential, advantages, and limitations. We will discuss future directions of organoid research in understanding cancer immunology in-depth and identifying novel I/O targets and treatment strategies.

Keywords: cancer; immunotherapy; organoid; tumour microenvironment.

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Conflict of interest statement

H.C.T. and S.V.S. are members of NeoTILa Pte Ltd. H.C.T. offers consultation for Tessa Therapeutics.

Figures

Figure 1
Figure 1
Schematics of air-liquid interface (ALI) culture and tissue slice culture (TSC) for ex vivo tumour: (a) ALI preserves the tumour-TME interaction with gentle tissue dissociation. BME: basement membrane extract. (b) TSC directly preserves sliced tissues as a whole. Figure created with BioRender.com.
Figure 2
Figure 2
Schematic of the bottom-up approach for creating liver tumour organoids. Figure created with BioRender.com.
Figure 3
Figure 3
Tabulated summary of different cell types in tumour organoids, the knowledge added, and the therapeutics tested. TAM: tumour-associated macrophage; EC: endothelial cell; CAF: cancer-associated fibroblast; ALI: air–liquid interface; DC: dendritic cell; MDSC: myeloid-derived suppressor cell; ICI: immune checkpoint inhibitor; IFN: interferon; iCAF: inflammatory CAF; myCAF: myofibroblastic CAF; TME: tumour microenvironment; CAR: chimeric antigen receptor.
See this image and copyright information in PMC

References

    1. Hodi F.S., O’Day S.J., McDermott D.F., Weber R.W., Sosman J.A., Haanen J.B., Gonzalez R., Robert C., Schadendorf D., Hassel J.C., et al. Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med. 2010;363:711–723. doi: 10.1056/NEJMoa1003466. - DOI - PMC - PubMed
    1. Hamid O., Robert C., Daud A., Hodi F.S., Hwu W.J., Kefford R., Wolchok J.D., Hersey P., Joseph R.W., Weber J.S., et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N. Engl. J. Med. 2013;369:134–144. doi: 10.1056/NEJMoa1305133. - DOI - PMC - PubMed
    1. Weber J.S., D’Angelo S.P., Minor D., Hodi F.S., Gutzmer R., Neyns B., Hoeller C., Khushalani N.I., Miller W.H., Jr., Lao C.D., et al. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): A randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2015;16:375–384. doi: 10.1016/S1470-2045(15)70076-8. - DOI - PubMed
    1. Garon E.B., Rizvi N.A., Hui R., Leighl N., Balmanoukian A.S., Eder J.P., Patnaik A., Aggarwal C., Gubens M., Horn L., et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N. Engl. J. Med. 2015;372:2018–2028. doi: 10.1056/NEJMoa1501824. - DOI - PubMed
    1. Hegde P.S., Chen D.S. Top 10 challenges in cancer immunotherapy. Immunity. 2020;52:17–35. doi: 10.1016/j.immuni.2019.12.011. - DOI - PubMed

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