Personalized immunotherapy may be one step closer for patients with cholangiocarcinoma (CCA), according to an article recently published in the British Journal of Cancer.

“As proof of principle, and likely supplemented with patient-specific immune cells, the co-culture method presented in this study could serve as a useful tool to examine the efficacy of new ICI [immune checkpoint inhibitors] and to predict which, if any, ICI would be most effective in individual patients,” the authors explained. 

The study aimed to evaluate the effectiveness and feasibility of using ICIs in CCA organoids and cells in a patient-specific manner. To achieve this, they collected tumoral tissue samples from 7 patients with liver cancer who had not received previous chemotherapy or other immunosuppressive drugs.


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The experiment involved coculturing CCA organoids with either T cells or mononuclear cells from peripheral blood samples to later analyze their behavior. Flow cytometry and time-lapse confocal images revealed an overall diminished amount of live organoid cells with noticeably higher apoptosis rates. Similarly, an increase in cytokeratin 19 fragment was also present.

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Results markedly varied among patients, further showcasing heterogeneity regarding the overall response of organoid lines upon contact with immune cells. For example, while CCA1 organoids exhibited resistance in direct and indirect experiments, CCA2 appeared susceptible to apoptosis in both settings. Additionally, T cells effectively targeted CCA3 in cocultures, but tumor-infiltrating leukocyte-conditioned media paradoxically stimulated these organoids.

These findings come as no surprise since CCA is characterized by its considerable heterogeneity, which further constitutes one of the most important challenges regarding its treatment and prognosis. The results reported in this article highlight the potential benefit of using personalized immune cells and CCA organoid cocultures for these patients.

“This novel 3D co-culture system allows for (1) maintaining the morphology and growth of CCA organoids, (2) survival and function of immune cells, (3) interaction between organoids and immune cells, and (4) quantifiable patient-specific cytotoxic effects of immune cells in CCA organoids,” the authors concluded.

Reference

Zhou G, Lieshout R, van Tienderen GS, et al. Modelling immune cytotoxicity for cholangiocarcinoma with tumour-derived organoids and effector T cells. Br J Cancer. Published online May 21, 2022. doi:10.1038/s41416-022-01839-x