Cancer and the Immune System 2023 PDF

The immune system and cancer Dr Felix N. Toka, DVM, PhD, DSc. Professor, Veterinary Immunology & Virology Department of Biomedical Sciences Objectives Define cancer Explain why tumor cells might trigger host immune responses Describe types of immune responses against tumo...

The immune system and cancer Dr Felix N. Toka, DVM, PhD, DSc. Professor, Veterinary Immunology & Virology Department of Biomedical Sciences Objectives Define cancer Explain why tumor cells might trigger host immune responses Describe types of immune responses against tumors Tumor evasion of the immune system What is cancer? cancer is a result of imbalances in the rates of cell division and cell death, i.e., tumors arise when cells divide more rapidly than they die  Development of tumors after development, many tumors may be eliminated by intrinsic mechanisms, but some are not. Tumor Antigens Antigens that are expressed on tumor cells but not on normal cells are called tumor-specific antigens Tumor antigens that are also expressed on normal cells are called tumor-associated antigens Immune response to tumors Host responses involve both innate and adaptive mechanisms Innate immune mechanisms Neutrophils - produce TNF-related apoptosis-inducing ligand, which stimulates apoptosis in tumor cells NK cells - express NKG2D which can bind MICA and MICB on many tumor cells Macrophages classically activated M1 macrophages can kill many tumor cells tumors are possibly recognized by DAMPs from dying tumor cells through macrophage TLRs activation of macrophages by IFN-γ produced by tumor-specific T cells they kill through production of nitric oxide (NO) M2 macrophages have been known to promote tumor growth through secretion of vascular endothelial growth factor (VEGF) and TGF-β Adaptive immune mechanisms CD8+ T cells - specific for tumor peptides presented on MHC class I can directly lyse tumor cells using perforins and granzymes CD4+ T cells can be activated by APCs presenting tumor antigens leading to direct or indirect destruction of the tumor IFN produced by CD4+ T cells activates macrophages NKT cells can recognize antigen presented by non-classical MHC class I molecules on tumor cells Antibodies Tumor-bearing hosts may produce antibodies against various tumor antigens Antibodies may mediate killing of tumor cells by activating complement or by … antibody-dependent cell-mediated cytotoxicity Tumor escape some tumor cells actively suppress host immune responses, e.g., TGF-β induces tumor cell proliferation and angiogenesis TGF-β suppresses elements of the host antitumor immune response Tumor-activated DCs secrete indoleamine 2,3- dioxygenase (IDO), which suppresses T-cell proliferation. Tumor cells often secrete galectin-1, which stimulates angiogenesis programmed cell death ligand 1 (PDL1), secreted by tumor cells may dramatically slow immune responses Mechanisms by which tumors escape T cell immune defenses Normal anti-tumor response Equilibrium maintain equilibrium, or steady state, in which tumor cells remain but do not progress tumor cells are not completely eliminated, but neither do they proliferate  Tumor immunoediting Tumor cells under the selection pressure of a normal immune system will be edited to yield tumor cells that can evade immunity. Tumors growing without an adaptive immune system, will remain immunogenic Immune evasion Tumor immunotherapy Adoptive transfer of in vitro activated immune cells T cell inhibitor blockade