Evasion of Immune Responses by Tumors
المؤلف:
Abbas, A. K., Lichtman, A. H., & Pillai, S
المصدر:
Basic Immunology : Function and disorders of immune system
الجزء والصفحة:
6th ed , page 200-202
2025-05-25
644
Immune responses often fail to check tumor growth because cancers evade immune recognition or resist immune effector mechanisms. The immune system faces daunting challenges in combating malignant tumors, because immune responses must kill all the tumor cells in order to be effective, and tumors can grow rapidly. Often, the growth of the tumor simply outstrips immune defenses. Not surprisingly, tumor cells that evade the host immune response are selected to survive and grow. Tumors use several mechanisms to avoid destruction by the immune system (Fig. 1):
• Some tumors stop expressing class I MHC molecules or molecules involved in antigen processing or MHC assembly, so they cannot display antigens to CD8+ T cells. Mutations affecting class I MHC–associated anti gen presentation are likely more effective at immune evasion than loss of tumor neoantigens because any tumor may express many immunogenic antigens, all of which would have to be mutated or lost, whereas mutation in any component of antigen presentation will lead to failure to present all antigens.
Fig1. How tumors evade immune responses. Antitumor immunity develops when T cells recognize tumor antigens and are activated. Tumor cells may evade immune responses by losing expression of anti gens or major histocompatibility complex (MHC) molecules or by producing immunosuppressive cytokines or ligands such as PD-L1 for inhibitory receptors on T cells. Tumors may also create an immunosuppressive microenvironment with regulatory T cells and antiinflammatory myeloid cells. CTL, Cytotoxic T lymphocyte, MDSC, myeloid derived suppressor cell.
• Tumors engage pathways that inhibit T cell activation. For example, many tumors express PD-L1, a ligand for the T cell inhibitory receptor programmed cell death protein 1 (PD-1). Furthermore, tumors, being persistent, cause repeated stimulation of T cells specific for tumor antigens. The result is that the T cells develop an exhausted state, in which they express high levels of PD-1, cytotoxic T lymphocyte associated antigen 4 (CTLA-4), and other inhibitory molecules, and become unresponsive to antigen.
• Factors in the tumor microenvironment may impair the ability of dendritic cells to induce strong antitumor immune responses. For example, dendritic cells that capture tumor antigens often express only low levels of B7 costimulators, resulting in preferential engagement of the inhibitory receptor CTLA-4 on naive T cells in the draining lymph nodes, rather than the stimulatory receptor CD28 . Some tumors may induce regulatory T cells, which also suppress antitumor immune responses. Myeloid-derived suppressor cells, which are developmentally related to neutrophils and monocytes but have mainly antiinflammatory functions, are abundant in tumors, and are believed to contribute to immunosuppression.
• Some tumors may secrete immunosuppressive cytokines, such as transforming growth factor β.
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