Lepton scattering is an established ideal tool for studying inner structure of small particles such as nucleons as well as nuclei. As a future high energy nuclear physics project, an Electron-ion collider in China (EicC) has been proposed. It will be constructed based on an upgraded heavy-ion accelerator, High Intensity heavy-ion Accelerator Facility (HIAF) which is currently under construction, together with a new electron ring. The proposed collider will provide highly polarized electrons (with a polarization of ∼80%) and protons (with a polarization of ∼70%) with variable center of mass energies from 15 to 20 GeV and the luminosity of (2–3) × 1033 cm−2 · s−1. Polarized deuterons and Helium-3, as well as unpolarized ion beams from Carbon to Uranium, will be also available at the EicC.The main foci of the EicC will be precision measurements of the structure of the nucleon in the sea quark region, including 3D tomography of nucleon; the partonic structure of nuclei and the parton interaction with the nuclear environment; the exotic states, especially those with heavy flavor quark contents. In addition, issues fundamental to understanding the origin of mass could be addressed by measurements of heavy quarkonia near-threshold production at the EicC. In order to achieve the above-mentioned physics goals, a hermetical detector system will be constructed with cutting-edge technologies.This document is the result of collective contributions and valuable inputs from experts across the globe. The EicC physics program complements the ongoing scientific programs at the Jefferson Laboratory and the future EIC project in the United States. The success of this project will also advance both nuclear and particle physics as well as accelerator and detector technology in China.

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.

Multiscale systems biology and systems pharmacology are powerful methodologies that are playing increasingly important roles in understanding the fundamental mechanisms of biological phenomena and in clinical applications. In this review, we summarize the state of the art in the applications of agent-based models (ABM) and hybrid modeling to the tumor immune microenvironment and cancer immune response, including immunotherapy. Heterogeneity is a hallmark of cancer; tumor heterogeneity at the molecular, cellular, and tissue scales is a major determinant of metastasis, drug resistance, and low response rate to molecular targeted therapies and immunotherapies. Agent-based modeling is an effective methodology to obtain and understand quantitative characteristics of these processes and to propose clinical solutions aimed at overcoming the current obstacles in cancer treatment. We review models focusing on intra-tumor heterogeneity, particularly on interactions between cancer cells and stromal cells, including immune cells, the role of tumor-associated vasculature in the immune response, immune-related tumor mechanobiology, and cancer immunotherapy. We discuss the role of digital pathology in parameterizing and validating spatial computational models and potential applications to therapeutics.