Modulation of Tumor Immunity by Soluble and Membrane-Bound Molecules at the Immunological Synapse

Figure 2

Activating and inhibiting immunological synapses for naïve and effector T cells. (a) APCs bear modulatory molecules on their surfaces that shape T cell activation and differentiation during IS assembly. Costimulatory molecules provide positive stimuli to T cells that are activating, while inhibitory molecules dampen T cell activation producing anergic or regulatory T cells. Tumor cells have been shown to express T cell inhibitory molecules on their surface to abrogate T cell activation or modulate their activity to produce inhibitory regulatory T cells. Cytokines and chemokines expressed by APCs or tumor cells can also modulate T cell activation synergizing or antagonizing with the above-mentioned membrane-bound molecules. Concentration of TCR/pMHC and adhesion molecules at the APC-T cell interface forms an immunological synapse. (b) CTLs exert their cytotoxic effects mainly through the release of soluble cell-killing molecules released towards target cells. Cytotoxic molecules include granule proteases known as granzymes aided by membrane-disruptive proteins known as perforins. Additionally, engagement of death receptors on the target cells, such as Fas (CD95) and TRAILR by FasL (CD95-ligand) and TRAIL molecules expressed on the surface of T cells, can also induce cell death mediated by apoptosis.