John Giannios

By John N. Giannios

Cancer immunoediting is composed of three phases: elimination, equilibrium, and escape. Tumor cells, which successfully navigate these phases, are capable of evading destruction by the immunity system of the host. Furthermore, there are different types of nonimmune surveillance against tumors, including genetic surveillance, which is based on DNA repair and checkpoint control, intracellular surveillance related to apoptosis or type I PCD, intercellular surveillance linked to the tumor microenvironment, and epigenetic surveillance related to the structure of chromatin, and specifically the stringency of imprinting. Circumventing immune destruction is one of the hallmarks of cancer pathogenesis, in addition to evading growth suppressors, deregulating cellular energetics, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, sustaining proliferative signaling, and resisting cell death, which may lead to the uncontrollable promotion of tumor burden at the expense of the immune system. Although immunoediting may eliminate tumor cells with alterations in their antigenic epitope profile, many immunoresistant variants escape from the immune system of the host by various immunosuppressive molecular and cellular mechanisms. There are many immunomodulatory effects of targeted therapies that can circumvent tumor-mediated immunosuppression, improving the effector T-cell function, which enhances eradication of targeted tumors. Another even more efficient antitumor strategy consists of combining targeted therapies with immunotherapies, which exert many antitumor synergies. The subsequent complex interplay of targeted anticancer agents and immunotherapy may sensitize tumor cells to immune-mediated eradication with long-lasting immunotherapeutic effects, which may inhibit induction of tumor dormancy. These combinatorial immunotherapies with targeted therapies can be used as neoadjuvants and adjuvant treatments with conventional anticancer strategies, such as surgical debulking, radiation therapy, and chemotherapy. In conventional anticancer treatment, the chemotherapeutic-induced immunosuppression inhibits the anticancer efficiency of cell therapies, which are based on activated lymphocytes for eradication of tumor cells, enhancing susceptibility to infections. The majority of conventional chemotherapeutic agents interfere with hematopoiesis and subsequently with the immune system, affecting the surveillance of cancer cells leading to the promotion of tumor development and growth. Furthermore, cancer surgery causes tremendous alterations in the neuroendocrine, metabolic, and immune systems constituting the stress response, which may lead to infection and cancer recurrence. Generally by using an integrative medicine immunotherapeutic approach, where alternative medicine practice which follows a multitargeted and bidirectional regulation may compensate for deficiencies of conventional orthodox western medicine, which is characterized by specificity, we may achieve a synergistic effect concerning circumvention of tumor-induced immunosuppression and enhancement of antitumor immunomodulation followed by minimization or elimination of side effects, prolonging the survival rate of advanced stage and metastatic cancer patients promoting their quality of life. The key is to treat each cancer patient under a personalized evidence-based medicine approach, which must rely on clinomics, including transcriptomics, genomics, immunomics, lipidomics, glycomics, proteomics, metabolomics, nutrigenomics, and mainly epigenomics whose alterations in their noncoding RNA genes are reversible especially with immunonutrition. The precise immunotherapeutic approach against cancer may act synergistically with conventional anticancer therapies, such as surgery, chemotherapy, and radiotherapy combined with therapies based on molecular targeting, which are tailored for each patient on a pharmacogenomic basis, and they can be combined with nanomedicine for specific molecular targeting and circumvention of biological milieu interactions, which may enhance tremendously therapeutic efficacy with simultaneous reduction of systemic toxicity.

Part of the book: Immunopathology and Immunomodulation