A computational multiscale agent-based model for simulating spatio-temporal tumour immune response to PD1 and PDL1 inhibition. Issue 134 (30th September 2017)

• Record Type: Journal Article
• Authors: Gong, Chang; Milberg, Oleg; Wang, Bing; Vicini, Paolo; Narwal, Rajesh; Roskos, Lorin; Popel, Aleksander S.
• Is Part Of: Journal of the Royal Society interface. Volume 14:Issue 134(2017)
• Publication Date: 2017-09-30
• Subjects: immuno-oncology -- immunotherapy -- immune checkpoint -- systems biology -- biomarker; Physical sciences -- Research -- Periodicals; Life sciences -- Research -- Periodicals; Interdisciplinary research -- Periodicals; 570.5
• DOI: 10.1098/rsif.2017.0320
• Languages: English
• ISSNs: 1742-5689

Abstract

Abstract : When the immune system responds to tumour development, patterns of immune infiltrates emerge, highlighted by the expression of immune checkpoint-related molecules such as PDL1 on the surface of cancer cells. Such spatial heterogeneity carries information on intrinsic characteristics of the tumour lesion for individual patients, and thus is a potential source for biomarkers for anti-tumour therapeutics. We developed a systems biology multiscale agent-based model to capture the interactions between immune cells and cancer cells, and analysed the emergent global behaviour during tumour development and immunotherapy. Using this model, we are able to reproduce temporal dynamics of cytotoxic T cells and cancer cells during tumour progression, as well as three-dimensional spatial distributions of these cells. By varying the characteristics of the neoantigen profile of individual patients, such as mutational burden and antigen strength, a spectrum of pretreatment spatial patterns of PDL1 expression is generated in our simulations, resembling immuno-architectures obtained via immunohistochemistry from patient biopsies. By correlating these spatial characteristics with in silico treatment results using immune checkpoint inhibitors, the model provides a framework for use to predict treatment/biomarker combinations in different cancer types based on cancer-specific experimental data.