Abstract
The significant contribution of host immunity in early tumorigenesis has been recently recognized as a result of our better understanding of the molecular pathways regulating tumor cell biology and tumor-lymphocyte interactions. Emerging evidence suggests that disseminated dormant tumor cells derived from primary tumors before or after immune surveillance, are responsible for subsequent metastases. Recent trends from the field of onco-immunology suggest that efficiently stimulating endogenous anticancer immunity is a prerequisite for the successful outcome of conventional cancer therapies. Harnessing the immune system to achieve clinical efficacy is realistic in the context of conventional therapies resulting in immunogenic cell death and/or immunostimulatory side effects. Targeted therapies designed to target oncogenic pathways in tumor cells can also positively regulate the endogenous immune response and tumor microenvironment. Identification of T cell inhibitory signals has prompted the development of immune checkpoint inhibitors, which specifically hinder immune effector inhibition, reinvigorating and potentially expanding the preexisting anticancer immune response. This anticancer immunity can be amplified in the setting of immunotherapies, mostly in the form of vaccines, which boost naturally occurring T cell clones specifically recognizing tumor antigens. Thus, a promising anticancer therapy will aim to activate patients’ naturally occurring anticancer immunity either to eliminate residual tumor cells or to prolong dormancy in disseminated tumor cells. Such an endogenous anticancer immunity plays a significant role for controlling the balance between dormant tumor cells and tumor escape, and restraining metastases. In this review, we mean to suggest that anticancer therapies aiming to stimulate the endogenous antitumor responses provide the concept of the therapeutic management of cancer.
Highlights
The endogenous immunological response during the natural course of cancer constitutes the concept of cancer immunomodulation as described in the “immunoediting” hypothesis almost 1.5 decades ago [1].The immunoediting process is based on the knowledge obtained from progresses in our understanding of mechanisms regulating tumor cell immune recognition and immune evasion
We have focused on the role of the immune system, as this is defined from endogenous antitumor responses, in controlling the process of tumor dormancy during the equilibrium phase
We do not know much about how this minimal residual disease (MRD) establishes and how long it persists before giving recurrences, what we have found out so far is that the immune equilibrium between the endogenous anticancer immune response and the dormant disseminated tumor cells is responsible for keeping the tumor from progressing
Summary
The endogenous immunological response during the natural course of cancer constitutes the concept of cancer immunomodulation as described in the “immunoediting” hypothesis almost 1.5 decades ago [1]. The equilibrium phase will progressively fade in the presence of epigenetic alterations, significantly affecting the biology of tumor cells, making them less immunogenic, highly suppressive, with a high angiogenic output This may seriously impact the balance between effector and regulatory cell compartments by favoring the infiltration and accumulation of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSC) within tumors. The immunoediting hypothesis provided an immune-mediated control of tumorigenesis by postulating opposing host-protective and tumor-promoting functions of the immune system Based on this theory, studies, later on, confirmed the role of endogenous adaptive antitumor immunity both as prognostic and predictive biomarkers [4,5]. The major role of the endogenous intratumoral immune reaction could improve our understanding of tumor evolution and have important consequences in clinical cure of cancer
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