Fig. 3. Boosting the intratumoural cancer immunity cycle.
By selecting therapeutic agents based on their immunological properties, local immunotherapy — achieved either directly through intratumoural administration or indirectly through selective delivery to or activation in the tumour following systemic administration — can specifically enhance each step of the cancer immunity cycle described by Chen and Mellman31. Examples of key cell types, processes and immunotherapy agents that are relevant to each step of this cycle are noted in the figure. Importantly, in accordance with steps 4 and 5 of the cycle, local immunotherapies need to result in redistribution of effector immune cells or antibodies via the circulation for abscopal or anenestic responses against distant untreated lesions and micrometastases. ADCs, antibody–drug conjugates; APCs, antigen-presenting cells; CAR, chimeric antigen receptor; CLEVER1, common lymphatic endothelial and vascular endothelial receptor 1 (also known as stabilin 1); PRR, pattern recognition receptor; Siglec-15, sialic acid-binding Ig-like lectin 15; SIRPα, signal-regulatory protein-α; TCR, T cell receptor, TILs, tumour-infiltrating lymphocytes; Treg, regulatory T.