Cd40 Cd40l

CD4+ helper

T lymphocyte

Phagocytosed tumor cell

Costimulator

Phagocytosed tumor cell

Costimulator

CD8+ T cell

Cytokines

CD8+ T cell

Differentiation of tumor-specific

Cytokines

Effector phase of anti-tumor CTL response

Tumor-specific CD8+ CTL

FIGURE 17-4 Induction of T cell responses to tumors. CD8+ T cell responses to tumors may be induced by cross-priming (cross-presentation), in which the tumor cells or tumor antigens are taken up, processed, and presented to T cells by professional antigen-presenting cells (APCs). In some cases, B7 costimulators expressed by the APCs provide the second signals for differentiation of CD8+ T cells. The APCs may also stimulate CD4+ helper T cells, which provide the second signals for CTL development. Differentiated CTLs kill tumor cells without a requirement for costimulation or T cell help. (The roles of cross-presentation and CD4+ helper T cells in CTL responses are discussed in Chapters 6 and 9.)

cross-priming, has been described in earlier chapters (see Chapter 6, Fig. 6-20). Once effector CTLs are generated, they are able to recognize and kill the tumor cells without a requirement for costimulation. A practical application of the concept of cross-priming is to grow dendritic cells from a patient with cancer, incubate the APCs with the cells or antigens from that patient's tumor, and use these antigen-pulsed APCs as vaccines to stimulate anti-tumor T cell responses.

The importance of CD4+ helper T cells in tumor immunity is less clear. CD4+ cells may play a role in anti-tumor immune responses by providing cytokines for effective CTL development (see Chapter 9). In addition, helper T cells specific for tumor antigens may secrete cytokines, such as TNF and IFN-y that can increase tumor cell class I MHC expression and sensitivity to lysis by CTLs. IFN-y may also activate macrophages to kill tumor cells. The importance of IFN-y in tumor immunity is demonstrated by the finding of increased incidence of tumors in knockout mice lacking this cytokine, the IFN-y receptor, or components of the IFN-y receptor signaling cascade.

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