LAUSR

Accelerating progress in tumor immunotherapy reflects a balance between what is particular to a given tumor and what cuts across tumor types and sites, including primary and metastatic brain tumors. Although there are tumor-specific differences, the epidermal growth factor receptor (EGFR) is an important target for both glioblastoma and non-small cell lung cancer, among others, making insight into basic EGFR biology broadly relevant (1). Indirect manipulation of the immune response acts even more broadly, with checkpoint inhibitors giving durable responses against the individual antigens expressed by multiple tumor types (2). Understanding of the nature of tumor antigen is still evolving. General insights into the practical requirements for specificity (3) and the importance of neo-antigens (2) complement identification of tumor-specific targets (4). Insights into tumor biology show a similar mix of the general and the specific. For any therapy, the eventual outgrowth of therapy-resistant tumor is common. Although resistance mechanisms vary, a general insight applies: it is now appreciated how often the potential for resistance, whether as clones with pre-existing mutations or as alternative regulatory states, is already present within the original tumor (5–8). Also appreciated is the importance of interactions between individual tumors and their local micro-environment (9–11), including those that favor immunosuppression. In this case, many details are also common, with many of the same components, such as regulatory T cells (Tregs) or cytokines (IL-10, etc.), implicated in the brain as other sites (Dutoit et al.; Perng and Lim).