Abstract
The tumor-immune interplay represents a dynamic series of events executed by cellular and soluble participants that either promote or inhibit successful tumor formation and growth. Throughout a tumor’s development and progression, the host organism’s immune system reacts by generating anti-cancer defenses through various incremental and combinatorial mechanisms, and this reactive orchestration is termed the cancer-immunity cycle. Success or failure of the cancer-immunity cycle dictates the fate of both host and tumor as winner or loser. Insights into how the tumor and host immune system continuously adapt to each other throughout the lifecycle of the tumor is necessary to rationally develop new effective immunotherapies. Additionally, the evolving nature of the cancer-immunity cycle necessitates therapeutic agility, requiring real-time serial assessment of immunobiologic markers that permits tailoring of therapies to the everchanging tumor immune microenvironment. In order to accelerate advances in the field of immuno-oncology, this review summarizes the steps comprising the cancer-immunity cycle, and underscores key breakpoints in the cycle that either favor cancer regression or progression, as well as shaping of the tumor microenvironment and associated immune phenotypes. Furthermore, specific large animal models of spontaneous cancers that are deemed immunogenic will be reviewed and proposed as unique resources for validating investigational immunotherapeutic protocols that are informed by the cancer-immunity cycle. Collectively, this review will provide a progressive look into the dynamic interplay between tumor and host immune responses and raise awareness for how large animal models can be included for developing combinatorial and sequenced immunotherapies to maximizing favorable treatment outcomes.
Highlights
Immuno-Oncology (IO) is a ballooning therapeutic landscape that holds great promise for improving long-term outcomes in both human and canine cancer patients
Given the spontaneous course of cancer development under operative immune mechanisms, pet dogs treated with interventional strategies at different steps of the cancerimmunity cycle have the potential to serve as valuable model systems for realizing the science and best clinical practices necessary in generating robust anticancer immune responses sufficient for improving the management of primary and metastatic tumor lesions [13, 15]
While not necessarily equivalent with translational relevance, six tumor histologies (Figure 2) including cutaneous histiocytoma, histiocytic sarcoma, transmissible venereal tumor, osteosarcoma, oral malignant melanoma, and canine mammary gland tumors will be highlighted for how the immune system participates in shaping the biology, clinical behavior, and prognosis of these tumors
Summary
Immuno-Oncology (IO) is a ballooning therapeutic landscape that holds great promise for improving long-term outcomes in both human and canine cancer patients. Given the spontaneous course of cancer development under operative immune mechanisms, pet dogs treated with interventional strategies at different steps of the cancerimmunity cycle have the potential to serve as valuable model systems for realizing the science and best clinical practices necessary in generating robust anticancer immune responses sufficient for improving the management of primary and metastatic tumor lesions [13, 15]. In Step 5, diapedesis opens the flood gates to infiltrating tumor-specific T cells into the TME, so that primed effector T cells can recognize and bind to tumor antigens presented on MHC class I molecules in Step 6 Together, this culminates to Step 7, in which cytotoxic T cells kill tumor cells via perforin and granzyme release or through FasL : Fas ligation. By incorporating serial biomarker assessments that accurately reflect the immune status of the tumor and microenvironment, it becomes possible to identify any defective step(s) in the cancer-immunity cycle and provides opportunity to restore normal functionality through directed immunotherapeutic interventions
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