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Review
. 2018 Feb;75(4):689-713.
doi: 10.1007/s00018-017-2686-7. Epub 2017 Oct 14.

CD4 and CD8 T lymphocyte interplay in controlling tumor growth

Dmitrij Ostroumov  1 , Nora Fekete-Drimusz  1 , Michael Saborowski  1 , Florian Kühnel  1 , Norman Woller  2
Affiliations
Review

CD4 and CD8 T lymphocyte interplay in controlling tumor growth

Dmitrij Ostroumov et al. Cell Mol Life Sci. 2018 Feb.

Abstract

The outstanding clinical success of immune checkpoint blockade has revived the interest in underlying mechanisms of the immune system that are capable of eliminating tumors even in advanced stages. In this scenario, CD4 and CD8 T cell responses are part of the cancer immune cycle and both populations significantly influence the clinical outcome. In general, the immune system has evolved several mechanisms to protect the host against cancer. Each of them has to be undermined or evaded during cancer development to enable tumor outgrowth. In this review, we give an overview of T lymphocyte-driven control of tumor growth and discuss the involved tumor-suppressive mechanisms of the immune system, such as senescence surveillance, cancer immunosurveillance, and cancer immunoediting with respect to recent clinical developments of immunotherapies. The main focus is on the currently existing knowledge about the CD4 and CD8 T lymphocyte interplay that mediates the control of tumor growth.

Keywords: Cancer mouse model; Cancer vaccine; Clinical study; Crosstalk; Immune escape; Immune response; Immunotherapy; Neoantigen; Oncolytic virotherapy; T cell exhaustion.

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Figures

Fig. 1
Fig. 1
Diverse strategies of the host have evolved to facilitate tumor suppression in different stages of malignancy. A dispensable healthy cell or a cell that acquired severe damage usually succumbs to apoptosis, a mechanism that is required to maintain cellular homeostasis. This can be regarded as an initial barrier of tumor development. Aberrant cell cycle activation leads to cellular senescence and initiates the extrinsic mechanism of senescence surveillance that limits cancer development. CD4 T cells and macrophages are the essential immune cells that mediate senescence surveillance of pre-malignant cells. When cells escape senescence surveillance and further proceed in their course of tumor development, they become malignant and are then subjected to cancer surveillance. In this phase, CD4 and CD8 T cell responses play a central role in mediating the elimination of malignant cells. T-cell-mediated cancer surveillance furthermore leads to cancer immunoediting that shapes tumors towards low immunogenicity
Fig. 2
Fig. 2
Failure of tumor rejection is often due to a malfunction within any step of the cancer immune cycle. Central components of this cycle are CD4 and CD8 T cells that are involved in all steps of the cycle. Crucial steps of the cancer immune cycle are outlined by the arrows. Any disruption of mutual CD4/CD8 T cell interplay or other crucial steps of T-cell-signaling within this circle that have been demonstrated to abort the whole cancer immune cycle are noted within the graphic representation. The figure comprises studies that have been discussed in this review and therefore does not provide a complete overview. All descriptions include the reference to original studies
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