Through this Notice of Special Interest (NOSI) on Exploratory Cancer Immunology Projects and Technologies (ExCITe), the National Cancer Institute intends to encourage R21 applications proposing innovative high-risk/high-reward research projects, that test novel hypotheses or develop novel technologies, to advance our understanding of cancer immunology. Research projects should focus on fundamental areas of cancer immunology, including innate and adaptive immune responses, tumor-immune ecosystems and their dynamic interactions, the immune response to metastases, systemic immune networks, immunosurveillance, tumor immune evasion, or immunomodulation. Projects should be distinct in scope and focus from those supported through the traditional R01 mechanism. ExCITe studies may involve considerable risk but have the potential to lead to research breakthroughs or the development of novel techniques, agents, methodologies, models, or applications that could have a major impact in cancer immunology and cancer immunotherapy research.