Figure 3.

Rational design of immunotherapeutic strategies through a comparative oncology approach including canine oral malignant melanoma as a model tumor for correcting potential breaks in the cancer-immunity cycle. Sequential or combinatorial interventions can be evaluated at each potential break within the cycle, starting with: Step 1 - release of melanoma antigens following immunogenic cell death; Step 2 - sufficient intratumoral dendritic cell/macrophage processing and presentation of melanoma antigens with subsequent migration to secondary lymphoid organs; Step 3 - effective priming and activation of naïve T lymphocytes; Step 4 - intravasation and extravasation of activated T lymphocytes through hematogenous and/or lymphatic routes; Step 5 - sufficient T lymphocyte infiltration through microenvironment and into melanoma parenchyma; Step 6 - T cell receptor engagement with melanoma MHC class I:peptides; and Step 7 - effector T lymphocyte killing of melanoma cells.