**Author details**

Krassimir Metodiev1\*, Paula Lazarova2,3, Jon Kyte2 , Gunnar Kvalheim2 and Jahn Nesland2

\*Address all correspondence to: kr.metod@yahoo.com

1 Dept. Preclinical and Clinical Sciences, Medical University, Varna, Bulgaria

2 Inst. Cancer Research, Univ. Hospital "Radium", Oslo, Norway

3 Clinical Laboratory, Univ. Hospital "St. Anna", Varna, Bulgaria

#### **References**


**Immunoediting, Immunosurveillance, Tumor-induced Immunosuppression and Immunoresistance, Immunomodulation, Immunotherapy, and Immunonutrition in Personalized and Precision Cancer Medicine**

John N. Giannios

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Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/61772

#### **Abstract**

Cancer immunoediting is composed of three phases: elimination, equilibrium, and es‐ cape. Tumor cells, which successfully navigate these phases, are capable of evading de‐ struction 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 strin‐ gency 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 sys‐ tem 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 en‐ hances eradication of targeted tumors. Another even more efficient antitumor strategy consists of combining targeted therapies with immunotherapies, which exert many an‐ titumor synergies. The subsequent complex interplay of targeted anticancer agents and immunotherapy may sensitize tumor cells to immune-mediated eradication with longlasting immunotherapeutic effects, which may inhibit induction of tumor dormancy. These combinatorial immunotherapies with targeted therapies can be used as neoadju‐

© 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.

vants 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, affect‐ ing the surveillance of cancer cells leading to the promotion of tumor development and growth. Furthermore, cancer surgery causes tremendous alterations in the neuroendo‐ crine, metabolic, and immune systems constituting the stress response, which may lead to infection and cancer recurrence. Generally by using an integrative medicine immu‐ notherapeutic approach, where alternative medicine practice which follows a multitar‐ geted 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 elim‐ ination 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 clinom‐ ics, including transcriptomics, genomics, immunomics, lipidomics, glycomics, proteo‐ mics, metabolomics, nutrigenomics, and mainly epigenomics whose alterations in their noncoding RNA genes are reversible especially with immunonutrition. The precise im‐ munotherapeutic 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 phar‐ macogenomic basis, and they can be combined with nanomedicine for specific molecu‐ lar targeting and circumvention of biological milieu interactions, which may enhance tremendously therapeutic efficacy with simultaneous reduction of systemic toxicity.

**Keywords:** Immunosurveillance, immunoediting, tumor-induced immunosuppression, immunoresistance, immunomodulation, immunotherapy, immunonutrition, personal‐ ized or precision cancer medicine, evidence-based medicine, omics

#### **1. Introduction**

The strategies to fight cancer are composed of mechanisms including surgery since 1600 BC, physics including radiotherapy since 1896, chemistry including chemotherapy since 1942, and biology including immunotherapy since 1976. Although immunotherapy has a long history that has been evaluated for more than a century, only recently has it entered a renaissance phase with anticancer biological agents, including the first monoclonal antibody approved in 1997, interleukin-2 (IL-2) cytokine approved in 1998, the first cellular immunotherapy as therapeutic vaccine approved in 2010, and the first checkpoint inhibitor approved in 2011, which has been succeeded by many more approved immunotherapeutic agents [1]. The cancer immunosurveillance hypothesis proposed by Ehrlich in 1909, modified by Burnet and Thomas in 1957, refers to the immunological resistance of the host against cancer development.
