Immune system overview
Key players in immune surveillance
T cell subsets: A promising focus for adoptive cancer immunotherapy
A fundamental principle of cancer immunology is that cancer cells express antigens that the immune system can recognize to target for cell elimination.
While there are a number of key players in this continual process of tumor immunosurveillance, T cells play an important role. T cells normally function to eliminate the body’s own cells that are infected or have become cancerous.
T cell subsets are defined by the cell-surface markers and transcription factors they express and the cytokines they secrete, and are grouped by function.
- CD4+ (helper) T cells
- CD8+ (cytotoxic) T cells
- Regulatory T (Treg) cells
- Gamma-delta (γδ) T cells
- Natural killer T (NKT) cells
T cell differentiation begins in the thymus, where the majority of immature cells express an alpha-beta (αβ) T cell receptor (TCR) and both CD4 and CD8 co-receptors.
Co-receptor binding with MHC determines an immature T cell’s differentiation into 2 main lineages
- CD4+ T cells result when the CD4 co-receptor binds to MHC class II, ceasing CD8 expression
- CD8+ T cells result when the CD8 co-receptor binds to MHC class I, ceasing CD4 expression
CD4+ T cells
Known as “helper” T cells because they help initiate and regulate immune responses. Each differentiated CD4+ subset releases specific cytokines that can support other immune cells and promote or suppress immune reactions.
Regulatory T (Treg) cells
A subset of either immature T cells or CD4+ T cells, Treg cells are responsible for inhibiting immune responses.
Gamma-delta (γδ) T cells
A minority of immature T cells express a gamma-delta TCR, and possess both innate and adaptive immune cell qualities with broad and potent anti-tumor activity, and both pro- and anti-inflammatory functions.
Tumor strategies to evade
T cell immune response
Lack of Immunogenic MoleculesTumor cells are heterogeneous, and some of them do not express the molecules necessary to trigger an immune response. When the immune system first begins to attack a tumor, malignant cells without these targeted molecules are able to survive and proliferate undetected by T cells.
Expression of Negative
Co-stimulatoryMoleculesTumors may express negative co-stimulatorymolecules that inhibit T cell activation. 24
Impaired Antigen PresentationTumor cells may have genetic mutations that prevent proper antigen processing and presentation, making recognition by T cells difficult.
Release of Cytokines That Impair
T CellFunctioningTumor cells can establish an immunosuppressive state within the microenvironment by releasing various immunosuppressive cytokines that inhibit T cellactivation. 24
Tumor evasion strategies can contribute to relapse and treatment resistance
In many cancer types, target cells are genetically diverse at diagnosis. Initial treatment with chemotherapy suppresses or kills the most aggressively multiplying cells but often leaves behind target cells with genetic mutations that allow them to continue multiplying despite ongoing therapy.
Back to top