Assia Konsoulova

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/61211

#### **Abstract**

The immune system and cancer coexist in close relationship which is an indispensable part of the processes of tumorigenesis, tumor growth, and metastatic spread. The elu‐ cidation and understanding of this continuous process could provide opportunities to develop strategies to impact the prognosis, and eventually to improve the cancer treatment process. Such strategies have been already implicated and proven efficient in the treatment of several tumor localizations such as malignant melanoma, lung and renal cancer. The present publication reviews the principles of cancer-related immune response, types and mechanisms of immune response and suppression, immunother‐ apy of solid tumors. We also discuss the pathways and the signaling molecules, par‐ ticipating in those immune response/suppression processes, turning them into potential targets and their actual and potential future role in the management of solid tumors. We focus on potential role and rationale for combination of immunothera‐ peutic and chemotherapeutic/targeted agents and radiotherapy in one treatment strat‐ egy.

**Keywords:** immune response, immune suppression, checkpoint inhibitors, immuno‐ therapy, solid tumors

#### **1. Introduction**

The relationship between the immune system and cancer has recently become a "modern topic" of interest in cancer research even though it was back in the early 1800s, when Virchow first described the presence of inflammatory cells in pathohistological tumor samples. Subsequently, Coley demonstrated that the use of bacterial products induced certain regres‐ sion in inoperable tumors [1]. It has been known for decades that the immune system plays an important role in the processes of inflammation, chronic inflammation, and cancer. Thus,

© 2015 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

scientific researchers continued the struggle to understand the role of Virchow's findings, aiming to link those processes. The elucidation of such relation could give an insight into the processes of tumorigenesis, tumor growth, and metastatic spread; it could potentially provide subsequent opportunities to develop strategies to impact the diagnosis, prognosis, and eventually to improve the cancer treatment process. The synallagmatic reciprocal talk between the host immune system and the tumor has been intensively studied. The processes of the host immune control over the tumor, immunoediting by the tumor, the immune escape, and the development of immune tolerance and suppression are described in this chapter. Our aim is also 1) to highlight the principles of cancer-related immune mechanisms, immunotherapy, and their role in the process of treatment of solid tumors; - and 2) to discuss the options to combine immunotherapeutic and chemotherapeutic agents trying to overcome the mechanisms of immune or inflammatory suppression and potentially improve cancer treatment strategies.

The initial immune-related therapies were aiming to activate the immune system and were represented by non-specific immunotherapies that didn't aim towards a specific target in the cancer cell (cytokines, interleukins, interferons, etc.). Subsequent efforts tried to identify antigens of the cancer cell and to design monoclonal antibodies (MAB), targeting those antigens. However, it has become clear that these therapies are failing because of the ability of cancers to induce immune tolerance, evasion, and suppression of the immune system, which created a new direction of research - to discover the pathways and the signaling molecules, participating in those immune suppression processes, thus turning them into potential targets as anticancer treatments.
