Sustained Coevolution in a Stochastic Model of Cancer-Immune Interaction.
George Jason T,Levine Herbert
The dynamic interactions between an evolving malignancy and the adaptive immune system generate diverse evolutionary trajectories that ultimately result in tumor clearance or immune escape. Here, we create a simple mathematical model coupling T-cell recognition with an evolving cancer population that may randomly produce evasive subclones, imparting transient protection against the effector T cells. T-cell turnover declines and evasion rates together explained differences in early incidence data across almost all cancer types. Fitting the model to TRACERx evolutionary data argued in favor of substantial and sustained immune pressure exerted upon a developing tumor, suggesting that clinically observed incidence is a small proportion of all cancer initiation events. This dynamical model promises to increase our quantitative understanding of many immune escape contexts, including cancer progression and intracellular pathogenic infections. SIGNIFICANCE: The early cancer-immune interaction sculpts intratumor heterogeneity through the selection of immune-evasive clones. This study provides a mathematical framework for investigating the coevolution between an immune-evasive cancer population and the adaptive immune system.
Immune cells within the tumor microenvironment: Biological functions and roles in cancer immunotherapy.
Lei Xu,Lei Yu,Li Jin-Ke,Du Wei-Xing,Li Ru-Gui,Yang Jing,Li Jian,Li Fang,Tan Hua-Bing
The immune cells within the tumor microenvironment (TME) play important roles in tumorigenesis. It has been known that these tumor associated immune cells may possess tumor-antagonizing or tumor-promoting functions. Although the tumor-antagonizing immune cells within TME tend to target and kill the cancer cells in the early stage of tumorigenesis, the cancer cells seems to eventually escape from immune surveillance and even inhibit the cytotoxic function of tumor-antagonizing immune cells through a variety of mechanisms. The immune evasion capability, as a new hallmark of cancer, accidently provides opportunities for new strategies of cancer therapy, namely harnessing the immune cells to battle the cancer cells. Recently, the administrations of immune checkpoint modulators (represented by anti-CTLA4 and anti-PD antibodies) and adoptive immune cells (represented by CAR-T) have exhibited unexpected antitumor effect in multiple types of cancer, bringing a new era for cancer therapy. Here, we review the biological functions of immune cells within TME and their roles in cancer immunotherapy, and discuss the perspectives of the basic studies for improving the effectiveness of the clinical use.