The continuum of cancer immunosurveillance: prognostic, predictive, and mechanistic signatures

Abstract

Numerous analyses of large patient cohorts identified specific patterns of immune activation associated with patient survival. We established these as the immune contexture, encompassing the type, functional orientation, density, and location of adaptive immune cells within distinct tumor regions. Based on the immune contexture, a standardized, powerful immune stratification system, the Immunoscore, was delineated. The immune contexture is characterized by immune signatures also observed in association with the broader phenomenon of immune-mediated, tissue-specific destruction. We defined these as the immunologic constant of rejection. Predictive, prognostic, and mechanistic immune signatures overlap, and a continuum of intratumor immune reactions exists. The balance between tumor cell growth and elimination may be tipped upon a crescendo induced by immune manipulations aimed at enhancing naturally occurring immunosurveillance. Here, we propose a broader immunological interpretation of these three concepts--immune contexture, Immunoscore, and immunologic constant of rejection--that segregates oncogenic processes independently of their tissue origin.