Integrating histopathology, immune biomarkers, and molecular subgroups in solid cancer: the next step in precision oncology

For many years, the gold standard cancer grading and staging had focused on the characteristics of the cancer cells and often disregarded the non-tumoral cell compartments. The expansion of research on the tumor immune microenvironment, the successes and dissemination of immunotherapies to treat cancer, and the open access to large -omic databases have allowed the development of novel powerful immune-based prognostic and theranostic biomarkers. Although they often correlate with histopathologic characteristics and TNM staging, in many instances, they are independently associated with, and potentially superior predictors of, the patient's prognosis and response to immunotherapies. As pathologists in the era of precision medicine, we are uniquely positioned to participate in the integration of these histologic and molecular features of the tumor microenvironment to provide the best prognostic information to clinicians and patients. In this review, we summarize some of the most important immune-related prognostic biomarkers in solid cancer, how they integrate with traditional histopathologic (i.e., staging and grading) and novel molecular stratification systems, and their potential role as predictors to response to agents blocking the PD-1/PD-L1 axis.