1 / 26

Cancer and Immune system

Cancer and Immune system. the second semester in 2016. Laboratory of Cellular Immunology Jeong Nara. Immune system.

mpeebles
Download Presentation

Cancer and Immune system

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Cancer and Immune system the second semester in 2016 Laboratory of Cellular Immunology Jeong Nara

  2. Immune system The immune system is the body’s defense system and its task is to protect the body against germs or degenerated cells (like cancer cells). The immune system is very complex. There are two component-ts: the cellular immune defense (for example “scavenger cells” and “killer cells”) and the complement system (“antibodies”, for example). http://6932024ba42556b26407-a85c761a6bd49913b8d52eb0d7ddeadd.r85.cf2.rackcdn.com/gitWVcXo6o_1398734967765.jpg http://www.airheads1.com/images/immune_system.jpg https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0072548/

  3. Immune system https://www.aids.gov/hiv-aids-basics/just-diagnosed-with-hiv-aids/hiv-in-your-body/immune-system-101/

  4. Immune system http://textbookofbacteriology.net/cellsindefenses75.jpg http://www.10forio.info/images/2_Immune-system/immune_cells_web.png Schiffrin EL, Immune mechanisms in hypertension and vascular injury. Clin Sci (Lond). 2014 Feb;126(4):267-74.

  5. Cancer Canceris a multistep process that results from the alterations in normal proliferation, differentiation and/or cell death mechanisms and has recently been associated with energy metabolism reprogram-ming and the evasion of immune destruction. D. Hanahan, R.a. Weinberg, Hallmarks of cancer: the next generation. Cell, 144 (5) (2011), pp. 646–674 Mendes F et al., The role of immune system exhaustion on cancer cell escape and anti-tumor immune induction after irradiation. Biochim Biophys Acta. 2016 Apr;1865(2):168-75.

  6. Immune surveillance Immune surveillance function executed by the immune system seems to represent an effective tumor suppressor mechanism, thus contributing to the incidence and progression of cancer. TAA : tumor associated antigen TA : tumor antigen Hiroki Ishii et al., THERAPEUTIC STRATEGY FOR CANCER IMMUNOTHERAPY IN HEAD AND NECK CANCER. Advances in Cellular and Molecular Otolaryngology 2015, 3: 27690. S.I. Grivennikov, F.R. Greten, M. Karin. Immunity, inflammation, and cancer. Cell, 140 (6) (2010), pp. 883–899. Mendes F et al., The role of immune system exhaustion on cancer cell escape and anti-tumor immune induction after irradiation. Biochim Biophys Acta. 2016 Apr;1865(2):168-75.

  7. Inflammation & Cancer Chronic and persistent inflammation strongly con-tributes to tumor initiation by generating genoto-xic stress and leading to cell proliferation, tumor progression, angiogenesis promotion and tissue invasion and, thus originating a favorable tumor microenvironment. Mendes F et al., The role of immune system exhaustion on cancer cell escape and anti-tumor immune induction after irradiation. Biochim Biophys Acta. 2016 Apr;1865(2):168-75. S.I. Grivennikov, F.R. Greten, M. Karin. Immunity, inflammation, and cancer. Cell, 140 (6) (2010), pp. 883–899.

  8. Inflammation & Cancer H. Yu, D. Pardoll, R. Jove. STATs in cancer inflammation and immunity: a leading role for STAT3. Nat. Rev. Cancer, 9 (11) (2009), pp. 798–809

  9. Immunosuppression & Cancer Cancer may have higher incidence when there is a concomitant reduction in the functionality of the immune system. Mendes F et al., The role of immune system exhaustion on cancer cell escape and anti-tumor immune induction after irradiation. Biochim Biophys Acta. 2016 Apr;1865(2):168-75. Hua Yu, Marcin Kortylewski & Drew Pardoll. Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment. Nature Reviews Immunology 7, 41-51 (January 2007)

  10. Immunosuppression & Cancer Mendes F et al., The role of immune system exhaustion on cancer cell escape and anti-tumor immune induction after irradiation. Biochim Biophys Acta. 2016 Apr;1865(2):168-75. Hua Yu, Marcin Kortylewski & Drew Pardoll. Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment. Nature Reviews Immunology 7, 41-51 (January 2007)

  11. Immunosuppression & Cancer MCA : chemical carcinogen methylcholanthrene Vijay Shankaran et al., IFNbig gamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 410, 1107-1111 (26 April 2001) R.D. Schreiber, L.J. Old, M.J. Smyth, Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science (New York, N.Y.), 331 (6024) (2011), pp. 1565–1570

  12. Immune system’s response Cancer Immunoediting normal tissue normal tissue restored Elimination of transformed cells immune system “Exhaustion” permitting cancer cells to rapidly proliferate and escape immune system activation and response to the cell transformation inhibition of the proliferation of transformed cells, Equilibrium clonal rapid proliferation of the “protected” transformed cells, immune system Th2 polarization, inhibition of cytotoxic immune cells, metastasis Mendes F et al., The role of immune system exhaustion on cancer cell escape and anti-tumor immune induction after irradiation. Biochim Biophys Acta. 2016 Apr;1865(2):168-75.

  13. Immune system’s response Equilibrium The immune system has the ability to eliminate tumor cells, but some cells survive becoming variants of previous existing cells, being poorly immunogenic and able to enter a steady-state phase. During the steady-state, cells of the adaptive immune system (CD4+, CD8+) as well as effector molecules (e.g. IFN-y, interleukin (IL)-12) are primarily responsible for preventing and inhibiting tumor development. Cytotoxic T Lymphocytes Mendes F et al., The role of immune system exhaustion on cancer cell escape and anti-tumor immune induction after irradiation. Biochim Biophys Acta. 2016 Apr;1865(2):168-75. Biochemistry, Genetics and Molecular Biology » "Cell Interaction", book edited by Sivakumar Gowder. Chapter 6 Cells, Molecules and Mechanisms Involved in the Neuro-Immune Interaction, By Rodrigo Pacheco, Francisco Contreras and Carolina Prado. Hiebert PR, Granville DJ. Granzyme B in injury, inflammation, and repair. Trends Mol Med. 2012 Dec;18(12):732-41.

  14. Immune system’s response Exhaustion & Evasion After equilibrium phase, two different mechanisms may emerge. One related with the immune system, that may become “exhausted”, losing the ability to eliminate cancer cells, meaning that they may proliferate actively without control. The other mechanism which may appear after the equilibrium phase is related with the acquisition of additional mutations by cancer cells under selective mechanisms. These cells will present a different phenotype, be poorly immunogenic, become immuno-evasive, more resistant to immune destruction and evade the immunological surveillance. Due to these alterations, cancer cells gain the capacity to metastasize. Mendes F et al., The role of immune system exhaustion on cancer cell escape and anti-tumor immune induction after irradiation. Biochim Biophys Acta. 2016 Apr;1865(2):168-75.

  15. Immune system’s response T cell Exhaustion Arne N. Akbar & Sian M. Henson, Are senescence and exhaustion intertwined or unrelated processes that compromise immunity? Nature Reviews Immunology 11, 289-295 (April 2011) Mendes F et al., The role of immune system exhaustion on cancer cell escape and anti-tumor immune induction after irradiation. Biochim Biophys Acta. 2016 Apr;1865(2):168-75.

  16. Immune system’s response T cell Exhaustion Mendes F et al., The role of immune system exhaustion on cancer cell escape and anti-tumor immune induction after irradiation. Biochim Biophys Acta. 2016 Apr;1865(2):168-75. Harvey RD, Immunologic and clinical effects of targeting PD-1 in lung cancer. Clin Pharmacol Ther. 2014 Aug;96(2):214-23.

  17. Immune system’s response T cell Exhaustion An important feature of immune system exhaustion in cancer is the loss of secretion of important mo-lecules such as IL-2, IFN-γ and TNF-α where the loss of production of IL-2 has a crucial role. IL-2 is se-creted under exposure to anti tumor specific antigen and can induce the proliferation of T cells, but, on the other hand, persistent exposure to tumor antigens can inhibit IL-2 production, allowing tumor pro-gression. Mendes F et al., The role of immune system exhaustion on cancer cell escape and anti-tumor immune induction after irradiation. Biochim Biophys Acta. 2016 Apr;1865(2):168-75. M.Y. Balkhi, Q. Ma, S. Ahmad, R.P. Junghans, T cell exhaustion and interleukin 2 downregulation. Cytokine, 71 (2) (2015), pp. 339–347

  18. Immune system & Radiotherapy Mendes F et al., The role of immune system exhaustion on cancer cell escape and anti-tumor immune induction after irradiation. Biochim Biophys Acta. 2016 Apr;1865(2):168-75.

  19. Immune system & Radiotherapy Danger signals such as calreticulin, high mobility group box 1 protein (HMGB1), ATP, and heat shock proteins (HSPs) are inducible by several chemotherapeutic drugs or irra-diation. They play important roles in the priming of anti-tumor immune responses. Mendes F et al., The role of immune system exhaustion on cancer cell escape and anti-tumor immune induction after irradiation. Biochim Biophys Acta. 2016 Apr;1865(2):168-75. A. Derer, L. Deloch, Y. Rubner, R. Fietkau, B. Frey, U.S. Gaipl, Radio-immunotherapy-induced immunogenic cancer cells as basis for induction of systemic anti-tumor immune responses — pre-clinical evidence and ongoing clinical applications. Front. Immunol., 6 (2015), p. 505.

  20. Immune system & Radiotherapy After RT a sequence of reactions occurs following a lesion of oncogenic cells, involving multiple me-chanisms of the immune system which can increase the positive feedback of the immune response against the tumor. Tumor cells respond to ionizing photons by upregulation of acute phase proteins, such as TNF-α, IL-1 and IL-6. MHC I molecules and adhesion molecules, such as intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) or E-selectin, are also upregulated in endothelial cells, co-ntributing to the recruitment of leukocytes through endothelial barriers nearby the tumor. Figure 2. Schematic of the immune response to RT. Tumor cells respond to ionizing RT by upregulating cytokines (TNFα, IL-1α/β and IL-6), adhesion molecules (ICAM-1, VCAM-1, E-selectin) and MHC Class I. Death of tumor cells also generates release of inflammatory molecules HMGB1 and ATP. This response recruits macrophages and DCs to tumors where they then receive activation signals resulting in their migration to draining lymph nodes where APCs (macrophages and dendritic cells) present tumor-derived antigens and stimulate T cell responses. Tumor-specific T cells then re-infiltrate tumors and induce death of damaged malignant cells. Mendes F et al., The role of immune system exhaustion on cancer cell escape and anti-tumor immune induction after irradiation. Biochim Biophys Acta. 2016 Apr;1865(2):168-75. S.L. Shiao, L.M. Coussens, The tumor-immune microenvironment and response to radiation therapy. J. Mammary Gland Biol. Neoplasia, 15 (4) (2010), pp. 411–421.

  21. Immunotherapy Adoptive cell transfer Nicholas P. Restifo et al., Adoptive immunotherapy for cancer: harnessing the T cell response. Nature Reviews Immunology 12, 269-281 (April 2012)

  22. Immunotherapy STAT3 Hua Yu, Marcin Kortylewski & Drew Pardoll. Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment. Nature Reviews Immunology 7, 41-51 (January 2007)

  23. Immunotherapy T cell inhibitory receptor Dendritic cell specific antitumour T cells become activated through TCR and CD28 signaling. CTLA-4 is subsequently upregulated and preferentially engages B7 to attenuate T-cell response. Ipilimumab blocks CTLA-4 function, thereby allowing enhanced T-cell stimulation and a more potent antitumour reaction. Ipilimumab may also antagonize CTLA-4 on regulatory T cells to limit their ability to suppress the antitumour T-cell effector response (not shown). Ira Mellman, George Coukos & Glenn Dranoff, Cancer immunotherapy comes of age. Nature 480, 480–489 (22 December 2011)

  24. Immunotherapy PD-1 & Tim-3

  25. Main Reference

  26. THANK YOU

More Related