Immuno-Oncology: Commiserating the Function and Abortive of the Immune System in Cancer: A Review
Department of Biotechnology, GIET College, JNTU Kakinada, Andhra Pradesh, India
- *Corresponding Author:
- Aparna Durga
Department of Biotechnology, GIET College
JNTU Kakinada, Andhra Pradesh, India
Received date: 05-07-2016; Accepted date: 20-07-2016; Published date: 25-07-2016
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The best capacity of the immune system is certain destruction of tumors with no toxicity to ordinary tissue and for lengthy-term reminiscence that may save you most cancers recurrence. Recent years of cancer immunology research have given robust evidence that most cancers lumps are identified with the aid of the immune system and their development can be immobilized or managed long term through a procedure referred to as immunosurveillance. Tumor specificity of the immune reaction is living inside the detection of tumor antigens.
Immunooncology, Immune system, Viral proteins, Antitumor, Immune suppression, Immunotherapy
Cancer immunotherapy is a new era of medicine that focused on the development and delivery of different types of immunotherapies that can improve the human body’s intrinsic potential in the generation of effective immune response against cancer. The main concentration of this field is only on immunity, not in the cancers cells. Scientists have been tried to know this complex interplay for over a century, with enticing however unsustainable results [1-8]. The Latest improvements in our expertise of antigen recognition, presentation and the cells required in T and B cellular activation have given new and excited immunotherapeutic strategies which can be used towards the cancer cells. Some achievement in animal models has been discovered and a few molecules are now being beneath medical trials. The interaction among our immune system and most cancers could be very complicated technique. Recent practices are based on agents that can disrupt the immune tolerance .
At present, numbers of immunotherapy having various mechanisms for cancer patients are beneath clinical trials.
Our Immune System and Cancer
The main function of our immune system is to recognize the difference between self and non self. Self is related to your body tissue and non-self is the foreign cells means any abnormal cell like viruses, bacteria, fungus and parasite [10-15]. Normally, your immune machine will not assault whatever that it identifies as a healthy a part of self. The hassle with cancer cells is they arise from our cells, but there are differences. As they grow and develop, cancer cells go through a series of mutations, turning into more and less like normal cells [16-23]. Sometimes our immune system can discover those variations and respond. Different instances, the most cancers cells slip via the defenses or are definitely able to inhibit the immune system [24-37]. Researchers have regarded for many years that our immune structures do recognize and attack most cancers cells (Figure 1). But, the progress being made nowadays in immunotherapy is the result of new understanding approximately the complicated interplay among the immune system and cancer. Immunooncology is also known as tumour immunology [38-51].
Figure 1: Immunotherapy for cancer.
Currently available Immunotherapy based treatments
Specifically, these mAbs are designed to target the cancer cells. These antibodies are used to block the growth and communication of tumor cells. The Food and drug administration is approved that by using these mAbs are helping to control the different types of cancers such as Breast cancer, colorectal cancer, Hodgkin’s lymphoma, Cervical Cancer, Brain cancer, Lung cancer, etc [52-69] (Figure 2).
Figure 2: Monoclonal antibodies.
A number of monoclonal antibody drugs are available to treat various types of cancer. Clinical trials are studying monoclonal antibody drugs in treating nearly every type of cancer.
Check point inhibitors/ Immune Modulators
As known that the immune system has the ability to recognize the differences between normal cells and foreign cells in this procedure it uses some cells as a checkpoint on certain immune cells that requisite to be activated or inactivated to begin immune response. Cancer cells sometimes find ways to use these checkpoints to avoid being attacked by the immune system .
Check point Inhibitors are two types one is CTLA-4 Inhibitors, used in the treatment of Melanoma and present research is going on the treatment of lung cancer and prostate cancer. Another check point called as PD-1/PD-L1Inhibitors. It is used in the advanced melanoma, lung cancer and a number of other cancers.
There are several types of inhibitors such as Atezolizumab (to treat bladder cancer), Ipilimumab (to treat melanoma of the skin), Pembrolizumab and Nivolumab. These drugs are helpful in the treatment of Hodgkin Lymphoma and non-small cell lung cancer.
These cancer vaccines are targeted the immune system to recognize and attack the certain markers, or antigens present in the cancer cells. There are different types of therapeutic vaccines in that some are made from individual proteins and others are made from whole cells. These vaccines are often required some additional substances to treat cancer called adjutants [71,72].
Provence is a therapeutic cancer vaccine and it is approved by FDA to treat the prostate cancer. BioVaxID is used in the treatment of Non-Hodgkin’s lymphoma and mantle cell lymphoma. Imprime PGG® is also type of cancer vaccine, used in the treatment of colorectal Cancer.
Oncolytic virus immunotherapies
The oncoloytic viruses are directly destroys the cancer cells and it triggers the cells of the immune system like T cells and dendritic cells (to target the cancer cells and eliminate the cancer throught the body) (Figure 3). Several types of viruses like adenovirus, retrovirus, measles and herpes simplex have now been clinically tested as oncoloytic agents [73-75].
Figure 3: Oncolytic virus.
Adoptive T cell transfer
It is an anti-cancer method, used to enhance the natural cancer- fighting ability of the body’s T cells by removing immune system cells. There are 3 types of methods.
• T cells are collected from patient’s tumor sample and multiplied in laboratory.
• It has taken from the body and it converts to genetically modified T cells to attack the antigens.
• When it can be taken from the patient’s body and apparelled with the receptors called chimeric antigen receptors (CARs); after those CARs can be given back to the patient, these “CAR T cells” recognize and attack cancer cells.
It has shown the result of metastatic melanoma, sarcoma and Neuroblastoma . Presently, the research is being investigated for use in the other type of tumors and blood cancer.
It is used to regulate the development and activity of the immune system cells, and also blood cells. These are classified as Interleukin and Interferon. It (IL’s) plays an important role in the cell division and Interferon [77-83], which enhance the capacity of certain immune cells to attack the antigens. These are used to treat the several types of benign tumors like Il-2 and IFN-alpha are used in the treatment of melanoma and Hairy cell leukemia, Cutaneous T cell lymphoma, Kaposi’s sarcoma [84-90].
Adjutant immunotherapies are substances that are either utilized alone or consolidated with different immunotherapies to improve the insusceptible reaction much more. Adjutant immunotherapies can enhance reactions to helpful growth immunizations that include in the work of T cells or other immune cells [91-95]. Some adjutant immunotherapies use ligands-molecules that can attach to protein receptors-to improve the immune responses. Granulocyte macro phage province empowering element is a cytosine that triggers the dendritic cells to create, and is frequently utilized as an adjutant with helpful disease immunizations, including those for prostate and pancreatic malignancy [96-100]. Toll-like receptors (TLRs) are utilized to build up the body's resistant reaction, and have uncovered the viability in cerebrum, kidney, lung and colon, pancreatic, prostate, ovarian and bosom malignancy.
The development of new immunotherapies against several diseases is based upon many years of scientist’s hard work to recognize the complex signaling pathways of immune systems and also they are trying to invent the new treatments that have the potential to change the ways in which treat cancer. Though the Immunooncology still developing and so many questions are raised but there is no specified answer still now. But in future may be Immunooncology will give the answer to all the questions and benefit the large numbers of cancer patients with minimum side effects.
- Finn OJ. Immuno-oncology: understanding the function and dysfunction of the immune system in cancer. Annals of Oncology. 2012;23:86-89.
- Alexander E and Olivera F. Advances in immuno-oncology. Annals of Oncology. 2012;23:85.
- Asher M. Pfizer expands hunt for immuno-oncology biomarkers. Nature Reviews Drug Discovery. 2016;15:77.
- Tai-Tsang C. Statistical issues and challenges in immuno-oncology. Journal of immunotherapy of cancer. 2013;1:18.
- Sarah W. Biomarker Development for Cancer Immuno-oncology/Immunotherapy: Simultaneous Digital Counting of Nucleic Acids and Proteins at 800-plex. The journal of immunooncology. 2016;196:18.
- David A. CD73–adenosine: a next-generation target in immuno-oncology. Immunotherapy. 2016;8:145-163.
- Rajni K. Primer on Immuno-Oncology and Immune Response. Clinical journal of oncology nursing. 2014;18:311-317.
- Axel H. The immuno-oncology framework. Oncoimmunology. 2012;1:334-339.
- Annie W. Integration of Immuno-Oncology and Palliative Care. Journal of clinical oncology. 2016; 34:1561-1562.
- Marc Hillairet DB. Evaluation of immuno-oncology related treatment in syngenic and human reconstituted immune systems. Cancer research. 2015;75:15.
- Matrana MR. Bladder Cancer Enters the Targeted Immunotherapy Age. Med Sur Urol. 2016;5:e114.
- Zanardi E, et al. Better Together: Immunotherapy as Future Combination Strategy for Breast Cancer. Immunother Open Acc. 2016;2:120.
- Bialkowski L and Thielemans K. Improving Anti-cancer Immunotherapy by Simultaneous Targeting Suppressive Tumor Microenvironment. J Vaccines Vaccin. 2016;7:324.
- Puéchal X. Immunotherapy in EosinophilicGranulomatosis with Polyangiitis: A New Step Forward?. J Vasc. 2016;2:e106.
- Pravettoni V, et al. Investigating the Changes in Venom-Specific IgE Induced by Wasp Venom Immunotherapy. J Clin Cell Immunol. 2016;7:416.
- Li G, et al. Potential of Radiofrequency Ablation in Combination with Immunotherapy in the Treatment of Hepatocellular Carcinoma. J Clin Trials. 2016;6:257.
- Shimodaira S, et al. An update on Dendritic Cell-Based Cancer Immunotherapy. Immunome Res. 2016;12:106.
- Paul I and Ghosh MK. Chaperones and Glioma Immunotherapy. J Cancer Sci Ther. 2016;8:069-070.
- Farrugia M and Baron B. Role of Regulatory T-cells in Oral Tolerance and Immunotherapy. Biochem Physiol. 2016;5:199.
- Cheriyan VT, et al. T cells in Immunobiology of Tumors and Immunotherapy. J Clin Cell Immunol. 2016;7:392.
- Yuqi Z and Manchao Z. Dynamic Duo: Synergy between Cancer Radiation Therapy and Immunotherapy. Immunother Open Acc. 2016;2:107.
- Yan J. Epigenetics and Immunotherapy: New Perspective for Breaking Chronic Viral Infection. Immunother Open Acc. 2016;2:106.
- Takeuchi K. Prophylactic Sublingual Immunotherapy for Japanese CedarPollinosis. Immunother Open Acc. 2016;2:e103.
- Kang K. Epigenetic Therapy, an Appealing Strategy to Improve Cancer Immunotherapy. J Immunooncol. 2015;1:102.
- Den Bergh JMJV, et al. Interleukin-15 and Interleukin-15 Receptor α mRNA-Engineered Dendritic Cells as Promising Candidates for Dendritic Cell-Based Vaccination in Cancer Immunotherapy. J Cancer Sci Ther. 2016;8:015-019.
- Shimodaira S, et al. Efficacy of Dendritic Cell-Based Cancer Immunotherapy. Biochem Anal Biochem. 2016;5:240.
- Matrana MR. Targeted Immunotherapy Breakthroughs in Renal Cell Carcinoma: Ushering in another New Era. Med Surg Urol. 2015;4:e113.
- Luljeta NA, et al. The Frequency of Influenza-Like Illness in Patients with Allergic Asthma on Immunotherapy. Immunome Res. 2015;11:103.
- Singh V, et al. Development of Novel Anti-Cd20 Monoclonal Antibodies and Modulation in Cd20 Levels on Cell Surface: Looking to Improve Immunotherapy Response. J Cancer Sci Ther. 2015; 7: 347-358.
- Luljeta NA, et al. The Frequency and Intensity of Bronchial Hyper-Reactivity in Patients with Allergic Asthma on Immunotherapy. Immunome Res. 2015;11:102.
- Jian-xin MA. 1,25-dihydroxyvitamin DÃ¢ÂÂ pretreatment enhances the efficacy of allergen immunotherapy in a mouse allergic asthma model. Chinese Medical Journal. 2010;123:3591-3596.
- Hsu JW, et al.1 alpha, 25-dihydroxylvitamin D3 promotes Bacillus Calmette-Guérin immunotherapy of bladder cancer. Oncotarget. 2013;4:2397-2406.
- April MA. A 1-day imported fire ant rush immunotherapy schedule with and without premedication. Allergy, Asthma & Immunology.2013;111:562-566.
- Rosenberg SA, et al. Cancer immunotherapy: moving beyond current vaccines. Nature medicine. 2004;10:909-915.
- Rosenberg SA, et al. A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science. 1986;233:1318-1321.
- Mathé G, et al. Active immunotherapy for acute lymphoblastic leukaemia. The Lancet. 1969;293:697-699.
- Bousquet J, et al. Allergen immunotherapy: therapeutic vaccines for allergic diseases A WHO position paper. Journal of Allergy and Clinical Immunology.1998;102:558-62.
- Schwartz RH. Costimulation of T Lymphocytes: MinireviewThe Role of 0D28, CTLA-4, and B7/BB1 in Interleukin-2 Production and Immunotherapy. Cell.1992;71:1065-1068.
- Rosenberg SA. Progress in human tumour immunology and immunotherapy. Nature. 2001;411:380-384.
- Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nature Reviews Cancer. 2012;12:252-264.
- Lajoie J, et al. Mucosal Immune Regulation: Does it Help Thwart HIV? J Clin Cell Immunol. 2012;S7:006.
- Agius LM. Putative Status of Actively Operative Performance Attributes as Determinants of Minimal Platform Oncogenesis in C-Myc Amplification. Adv Cancer Prev. 2016;1:108.
- Agius LM. Dimensions of Cooperative Cervical Oncogenesis in Abortive Infection by Human Papillomavirus. Cervical Cancer. 2016;1:109.
- Guan J, et al. Vector-Based let-7a miRNAsFunction as Suppressors of Multiple Oncogenes in SK-N-MC and SHEP Neuroblastoma Cells. J CarcinogMutagene. 2016;7:248.
- Procino A. HOX Genes and Oncogenesis. J Mol Genet Med. 2014;8:134.
- Chang S, et al. Luciferase Expression is more Accurate than GFP to Assess Mirnas-Relevant Oncogenesis in vivo Live Imaing Study. Cell Mol Biol. 2014;60:104.
- Ozen M and Karatas OF. MicroRNAs, as Essential Components of Non-Coding Genome, are Emerging Key Players of Oncogenesis. Mol Biol. 2013;2:e112.
- Mendes RA. Head and Neck Oncogenesis - An Evolving Conundrum with Molecular Shades. J Carcinog Mutagen. 2013;S5:e001.
- Monzavi-Karbassi B, et al. Obesity, Diabetes and Breast Cancer: Defining Metabolic Oncogenesis. J ObesWt Loss Ther. 2012;2:e108.
- Majeed R, et al. Therapeutic Targeting of Cancer Cell Metabolism: Role of Metabolic Enzymes, Oncogenes and Tumor Suppressor Genes. J Cancer Sci Ther. 2012;4:281-291.
- Auphan N, et al. Immunosuppression by glucocorticoids: inhibition of NF-kappaB activity through induction of IkappaB synthesis. Science. 1995;270:286.
- Lord GM, et al.Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature. 1998;394:897-901.
- Scheinman RI, et al. Role of transcriptional activation of IkappaBalpha in mediation of immunosuppression of glucocorticoids. Science. 1995;270:283.
- Nakamura K, et al. Cell contact–dependent immunosuppression by CD4+ CD25+ regulatory T cells is mediated by cell surface–bound transforming growth factor β. The Journal of experimental medicine. 2001;194:629-644.
- Ren G, et al. Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell stem cell. 2008;2:141-150.
- D'Haens G, et al. Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial. The Lancet. 2008;371:660-667.
- Swinnen LJ, et al. Increased incidence of lymphoproliferative disorder after immunosuppression with the monoclonal antibody OKT3 in cardiac-transplant recipients. New England Journal of Medicine. 1990;323:1723-1728.
- Sullivan KM, et al. Chronic graft-versus-host disease in 52 patients: adverse natural course and successful treatment with combination immunosuppression. Blood. 1981;5:267-276.
- Bunjes D, et al. Cyclosporin A mediates immunosuppression of primary cytotoxic T cell responses by impairing the release of interleukin 1 and interleukin 2. European journal of immunology. 1981;11:657-661.
- Nalesnik MA, et al. The pathology of posttransplantlymphoproliferative disorders occurring in the setting of cyclosporine A-prednisone immunosuppression. The American journal of pathology. 1988;133:173.
- Lee G, et al. Two Distinct Humanized Monoclonal Antibodies for Immunotherapy of Ovarian Cancer. J Cancer Sci Ther. 2014;6:110-116.
- Ratnaparkhe S, et al. Analyses using Cell Wall Glycan-directed Monoclonal Antibodies Reveal Xylan-degradation by Two Microbial Glycosyl Hydrolases in Cell Walls from Poplar and Switchgrass Biomass. J BioremedBiodeg. 2013;S4:004.
- Yokota S, et al. Pathogenesis of Systemic Inflammatory Diseases in Childhood: “Lessons From Clinical Trials of Anti-Cytokine Monoclonal Antibodies for Kawasaki Disease, Systemic Onset Juvenile Idiopathic Arthritis, and Cryopyrin-Associated Periodic Fever Syndrome”. PediatTherapeut 2013;3:171.
- Svobodova Z, et al. Dot-ELISA Affinity Test: An Easy, Low-Cost Method to Estimate Binding Activity of Monoclonal Antibodies. J Anal Bioanal Tech. 2013;4:168.
- Kuzmina NA, et al. Conservation of Binding Epitopes for Monoclonal Antibodies on the Rabies Virus Glycoprotein. J AntivirAntiretrovir. 2013;5:037-043.
- Bhuvaneswari R, et al. Combined use of anti-VEGF and anti-EGFR Monoclonal Antibodies with Photodynamic Therapy Suppresses Tumor Growth in an In vivo Tumor Model J Cancer Sci Ther 2013;5:100-105.
- Naujokat C. Targeting Human Cancer Stem Cells with Monoclonal Antibodies. J Clin Cell Immunol. 2012;S5:007.
- Valdés R, et al. Assessment of a Protein-Free Medium Performance in Different Cell Culture Vessels using Mouse Hybridomas to Produce Monoclonal Antibodies. Pharmaceut Anal Acta 2012;3:155.
- Sahli N, et al. Impact of Brachytherapy in the Treatment of Locally Advanced Cervical Cancer: Results from a Single Institution. GynecolObstet (Sunnyvale). 2016;6:386.
- Salmen S and Berrueta L. Immune Modulators of HIV Infection: The Role of Reactive Oxygen Species. J Clin Cell Immunol. 2012;3:121.
- Dunn GP, et al. Cancer immunoediting: from immunosurveillance to tumor escape. Nature immunology. 2002;3:991-998.
- Dunn GP, et al. The immunobiology of cancer immunosurveillance and immunoediting. Immunity. 2004;21:137-148.
- Zitvogel L, et al. Cancer despite immunosurveillance: immunoselection and immunosubversion. Nature Reviews Immunology. 2006;6:715-727.
- Garrido F, et al. Implications for immunosurveillance of altered HLA class I phenotypes in human tumours. Immunology today. 1997;18:89-95.
- Watson NF, et al. Immunosurveillance is active in colorectal cancer as downregulation but not complete loss of MHC class I expression correlates with a poor prognosis. International journal of cancer. 2006;118:6-10.
- Smyth MJ, et al. Cancer immunosurveillance and immunoediting: the roles of immunity in suppressing tumor development and shaping tumor immunogenicity. Advances in immunology. 2006;90:1-50.
- Paul P, et al. HLA-G expression in melanoma: a way for tumor cells to escape from immunosurveillance. Proceedings of the National Academy of Sciences. 1998;95:4510-4515.
- Taieb J, et al. A novel dendritic cell subset involved in tumor immunosurveillance. Nature medicine. 2006;12:214-219.
- Waldhauer I and Steinle A. NK cells and cancer immunosurveillance. Oncogene. 2008;27:5932-5943.
- Terabe M, et al. A nonclassical non-Vα14Jα18 CD1d-restricted (type II) NKT cell is sufficient for down-regulation of tumor immunosurveillance. The Journal of experimental medicine. 2005;202:1627-1633.
- Zhang WP and Zhu SM. The Effects of Inverse Ratio Ventilation with PEEP on Respiratory Function and Inflammatory Cytokines in Patients during One-lung Ventilation. J PulmRespir Med. 2016;6:329.
- Di H, et al. The Role of Inflammatory Cytokines in the Pathogenesis of Cerebral Palsy. GynecolObstet(Sunnyvale). 2016;6:360.
- Liu Z, et al. The Role of Orexin in the Effect of Electroacupuncture on Inflammatory Cytokines and Respiratory Regulations in a Rat Model of Smoke Induced Chronic Obstructive Pulmonary Disease: A Short Review. J Yoga Phys Ther. 2016;6:225.
- Venkateswaran N, et al. Overexpression of Pro-Inflammatory Cytokines in Myelodysplastic Syndrome (MDS-RA). J HematolThrombo Dis. 2016;4:231.
- Lotti T, et al. New Winning Strategies for Vitiligo: The Low Dose Cytokines Therapy Approach. Pigmentary Disorders. 2015;2:229.
- Pushparani DS. Role of Cytokines in Periodontal Wound Healing Process - A Review. Pharm Anal Chem Open Access. 2015;1:106.
- Alcántara Quintana LE, et al. The Antioxidant Activity of Peptides Isolated from Amaranthus on Normal Human Skin in vitro and Inflammatory Cytokines Detection. J Nutr Food Sci. 2015;5:419.
- Ahmad R, et al. Relationship of Il-5 with Th1 and Th2 Cytokines in Individuals with or without Type-2 Diabetes. J GlycomicsLipidomics. 2015;5:134.
- Cerny KL, et al. Differential Expression of mRNA Encoding Cytokines and Chemokines in the Reproductive Tract after Infection of Mice with Chlamydia trachomatis. Reprod Syst Sex Disord 2015;4:1000152.
- Singh SK and Prasad KN. Immunopathogenesis of Neurocysticercosis: Role of Cytokines. Immunome Res. 2015;11:096.
- Rimsza LM, et al. Loss of MHC class II gene and protein expression in diffuse large B-cell lymphoma is related to decreased tumor immunosurveillance and poor patient survival regardless of other prognostic factors: a follow-up study from the Leukemia and Lymphoma Molecular Profiling Project. Blood. 2004;103:4251-4258.
- Land H, et al. Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature. 1982;304:596-602.
- Bos JL. Ras oncogenes in human cancer: a review. Cancer research. 1989;49:4682-4689.
- Land H, et al. Cellular oncogenes and multistep carcinogenesis. Science. 1983;222:771-778.
- Hanahan D. Heritable formation of pancreatic beta-cell tumours in transgenic mice expressing recombinant insulin/simian virus 40 oncogenes. Nature. 1984;315:115-122.
- Morgan JI and Curran T. Stimulus-transcription coupling in the nervous system: involvement of the inducible proto-oncogenes fos and jun. Annual review of neuroscience. 1991;14:421-451.
- Zarbl H, et al. Direct mutagenesis of Ha-ras-1 oncogenes by N-nitroso-N-methylurea during initiation of mammary carcinogenesis in rats. Nature. 1985;315:382-385.
- Slamon DJ, et al. Expression of cellular oncogenes in human malignancies. Science. 1984;224:256-262.
- Weinstein IB. Addiction to oncogenes--the Achilles heal of cancer. Science. 2002;297:63-64.
- Zhang B, et al. microRNAs as oncogenes and tumor suppressors. Developmental biology. 2007;302:1-2.