The Immune System in Cancer Pathogenesis: Potential Therapeutic Approaches

Abstract

Interplay among immune activation and cancer pathogenesis provides the framework for a novel subspecialty known as immunooncology. In the rapidly evolving field of immunooncology, understanding the tumor-specific immune response enhances understanding of cancer resistance. This review highlights the fundamentals of incorporating precision medicine to discover new immune biomarkers and predictive signatures. Using a personalized approach may have a significant, positive impact on the use of oncolytics to better guide safer and more effective therapies.

Figure 1

Overview of the immune system: innate and adaptive immunity. An evolutionary bridge between both forms of immunity is observed due to the presence of γδ T cells, NKT cells, NK cells, dendritic cells, macrophages, and complement proteins. The innate immune responses include cells and soluble components that are nonspecific, fast-acting, and first responders in inflammation. In contrast, adaptive immunity encompasses immune components that are more specific for targeted antigens and capable of forming immunological memory [25, 27, 38].

Figure 2

The cancer immunoediting process. There are three phases in the cancer immunoediting process: elimination, equilibrium, and escape [4]. Elimination phase involves effector function of the immune cells to target and eradicate cancer. In the equilibrium phase a balance is obtained between progression of cancer and cancer elimination by the immune system. If the cancer persists then it overwhelms the immunity and escapes to go on and metastasize to the other organs [4, 40, 53].

Figure 3

Immunotherapies in cancer. Several FDA approved immunotherapies have been approved in the market to prevent or control cancer progression [1]. On APCs (such as B cells), monoclonal antibodies targeting CD20 (Rituximab) results in downregulation of B cell activity [62]. Other antigen-presenting cells (macrophages and dendritic cells) are also activated by Imiquimod, a small molecule agonist for TLR7 [1]. For activation of T cells Keytruda (monoclonal antibody targeting PD-L1- PD-1 interaction) and Ipilimumab (antibody against CTLA4) are approved and in clinical use [1, 39]. Recombinant cytokines such as Proleukin (IL-2), Leukine (GM-CSF), and Filgrastim (G-CSF) are approved for stimulation/activation of T cells, myeloid cells, and neutrophils, respectively [1, 67].