Out"FOX"ing cancer: the implications of FOXC2 as a putative predictive biomarker for cancer immunotherapy

The forkhead box family transcription factor FOXC2 is an important oncogenic driver of several hallmarks of cancer progression. In addition to its well-characterized roles in tumor angiogenesis, metabolic adaptation, and the epithelial-mesenchymal transition that precedes invasion and metastasis, FOXC2 has recently been implicated in tumor immune evasion as well. This Perspective article highlights recent findings concerning the potential value of FOXC2 as a predictive biomarker for cancer immunotherapy and brings attention to data connecting FOXC2 dysregulation to critical determinants of anti-tumor immune outcome, including influences on the makeup of the tumor immune microenvironment and cancer cell responsiveness to type I and type II interferons. In summarizing the current state of knowledge surrounding the immunologic impact of FOXC2 dysregulation in cancer, this article also raises several important questions that will need to be addressed going forward as the field aims to better understand FOXC2's role in tumor immune evasion so that these insights may be leveraged into translatable interventions that enhance the efficacy of cancer immunotherapy.