The identification of immunologic biomarkers associated with clinical response after immune intervention for cancer is an area of intensive investigation. The field would benefit from a more systemic and directed approach for biomarker identification and evaluation. Lessons can be learned from other fields, such as cancer diagnostics, as to how to develop response-associated biomarkers. Studies in both human in vitro models as well as murine models of cancer can significantly inform and streamline the choice of candidates. Adoptive T-cell therapy is an interesting model for exploring potential immunologic surrogates that may predict clinical response. Most likely the clinical effectiveness of immune-based treatments will be predicted by panels of markers rather than single assays of a specific immune effector cell.