Tracing the Equilibrium Phase of Cancer Immunoediting in Epidermal Neoplasms via Longitudinal Intravital Imaging

Abstract

Recognition of transformed cells by the immune system can sometimes generate a rate-limiting equilibrium phase, wherein tumor outgrowth is prevented without complete neoplasm elimination. Targeting premalignancies during this immune-controlled bottleneck is a promising strategy for rational cancer prevention. Thus far, immune equilibrium has been difficult to model in a traceable way, and most immunoediting systems have been limited to mesenchymal tumor types. Here, we introduce a mouse model for fluorescent tracing of somatic epithelial transformation. We demonstrate that transplantation can be used to prevent a confounding artificial tolerance that affects autochthonous inducible models. Using this system, we observe the expected dichotomy of outcomes: immune-deficient contexts permit rapid tumorigenesis, whereas initiated clones in immunocompetent mice undergo elimination or equilibrium. The equilibrium phase correlates with localization within hair follicles, which have been characterized previously as relatively immune-privileged sites. Given this, we posit that valleys in the immune surveillance landscape of a normal tissue can provide a cell-extrinsic alternative to the canonical cell-intrinsic adaptations believed to establish the equilibrium phase. Our model is a prototype for tracing immunoediting in vivo and could serve as a novel screening platform for therapies targeted against immune-controlled premalignancies.