www.astesj.com 773 Efficacy of multiple anticancer therapies may depend on host immune response Kritika Karri 1, 2* , Dhundy R Bastola 1 1 University of Nebraska at Omaha, College of Information Science and Technology, 68182, USA 2 Boston University, Bioinformatics Graduate Program, 02215, USA A R T I C L E I N F O A B S T R A C T Article history: Received: 05 April, 2017 Accepted: 16 May, 2017 Online: 16 June, 2017 The host immune system is a key player in anticancer therapy response and resistance. Although the impact of host immune response in the ‘war against cancer’ has been studied and it has been the basis for immunotherapy, understanding of its role in attenuating the action of conventional anticancer therapies is an area that has not been fully explored. In spite of advances in systemic therapy, the 5-year survival rate for adenocarcinoma is still a mere 13% and the primary reason for treatment failure is believed to be due to acquired resistance to therapy. Hence, there is a need for identifying reliable biomarkers for guided treatment of lung and colon adenocarcinoma and to better predict the outcomes of specific anticancer therapies. In this work, gene expression data were analyzed using public resources and this study shows how host immune competence underscores the efficacy of various anticancer therapies. Additionally, the result provides insight on the regulation of certain biochemical pathways relating to the immune system, and suggests that smart chemotherapeutic intervention strategies could be based on a patient’s immune profile. Keywords: Biomarker Immune response Progressive Disease Complete Remission Lung adenocarcinoma Colon adenocarcinoma Alkylating agents Antimetabolite Mitotic inhibitors Anti-angiogenesis GSEA 1. Introduction Cancer immunology has been studied and researched over many years to unravel the key mechanisms that determine therapeutic synergy or antagonism for cancer patients based on individual host immune environments. Traditional chemotherapy and other targeted therapies have been effective in combating many types of cancer. However, the efficacy of these interventions is determined by off-target effects within the host immune system [1]. Review of the literature shows that host immune response is key to the success of anticancer therapies through a process known as immune-surveillance [2]. Studies have shown that type-1 interferon can convert tumor associated macrophages (TAMs) into tumor-antagonizing macrophages by up-regulating the expression of dendritic cells in breast cancer. This results in increased CD8+ T cell population with reduced tumor growth and metastasis. As such, the combination of chemotherapy together with drugs that repolarize TAMs may be exploited to achieve greater patient responses and prevent resistance mechanisms within the immune system [3]. Some chemotherapeutics skew the polarization of macrophages directly, or indirectly via regulating cancer cell secreted factors [4]. FOXP3 expressing regulatory T cells (Tregs) are well-known for their immunosuppressive function in tumors [5]. They are a subset of CD4+ T cell population, which are involved with adaptive immune response. Tregs are known to be sensitive to cyclophosphamide and their depletion improves the potency of platinum-containing chemotherapeutic drugs against lung adenocarcinoma [6]. Another study has shown that Interleukin-17 (IL-17) producing CD4+ T cells limit the ability of 5-Flouro Uracil (5-FU) to delay the growth of subcutaneous thymoma cells. In contrast, IL-17 elevates the therapeutic efficacy of doxorubicin in sarcoma. Hence, the mode of action of these CD4+ T cell is paradoxical and depends widely on the cancer type [6]. However, their manipulation may be a useful strategy to determine the efficacy of chemotherapy. ASTESJ ISSN: 2415-6698 * Kritika Karri, College of Information Science and Technology, University of Nebraska at Omaha, 68182, USA, Email: kkarri@unomaha.edu Advances in Science, Technology and Engineering Systems Journal Vol. 2, No. 3, 773-787 (2017) www.astesj.com Special Issue on Recent Advances in Engineering Systems https://dx.doi.org/10.25046/aj020398