Cytokines in cancer pathogenesis and cancer therapy


The mixture of cytokines that is produced in the tumour microenvironment has an important role in cancer pathogenesis. Cytokines that are released in response to infection, inflammation and immunity can function to inhibit tumour development and progression. Alternatively, cancer cells can respond to host-derived cytokines that promote growth, attenuate apoptosis and facilitate invasion and metastasis. A more detailed understanding of cytokine–tumour-cell interactions provides new opportunities for improving cancer immunotherapy.

Key Points

  • Immune-cell infiltrates constitute a prominent component of the host response to cancer in some cases, but their functional significance remains incompletely understood.

  • Cancer cells express antigens that can be recognized by both the innate and adaptive immune systems.

  • Host-derived cytokines can suppress tumour formation by controlling infection, inflammation and immunity.

  • Tumour cells can exploit host-derived cytokines to promote growth, increase resistance to apoptosis and foster dissemination.

  • The systemic administration of cytokines can elicit antitumour effects, but the toxicities that are associated with this treatment often resemble a state of severe infection and can therefore be limiting.

  • Tumour cells can be genetically modified to express particular cytokines that stimulate the host immune response, thereby acquiring the capacity to function as cancer vaccines.

  • Antibody blockade of the CTLA-4 inhibitory receptor on T cells is a promising strategy to increase the potency of cancer vaccines, albeit with a risk of compromising tolerance to self-antigens.

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Figure 1: The innate and adaptive immune response.
Figure 2: Direct and indirect pathways of cancer recognition.
Figure 3: A coordinated cellular and humoral reaction mediates tumour destruction.
Figure 4: GM-CSF-secreting tumour-cell vaccines and CTLA-4 antibody blockade show synergistic antitumour effects.


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Supported by National Institutes of Health grants and the Leukemia and Lymphoma Society.

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A form of bioregulation in which a secretory factor affects only the cell from which it was secreted.


A form of bioregulation in which a cytokine that is released from one cell triggers a specific response from another cell in the microenvironment.


A set of plasma proteins, activated as a proteolytic cascade, that functions to coat the surface of microbes, thereby stimulating their lysis or phagocytosis.


A subset of lymphocytes that develops in the thymus and recognizes peptides that are presented by major histocompatibility class II antigens. These cells produce a wide range of cytokines that enhance B-cell antibody production and CD8+ T-cell and macrophage cytotoxic function.


A subset of lymphocytes that develops in the thymus and recognizes peptides presented by major histocompatibility class I antigens. These cells kill targets primarily through the perforin–granzyme pathway and death ligands such as FAS and tumour-necrosis factor.


(MHC). Locus of genes that encode a set of highly polymorphic membrane glycoproteins that present processed peptides to T-cell receptors.


A minor population of thymic-derived lymphocytes that express a heterodimeric γδ T-cell receptor. These lymphocytes can respond to glycolipid antigens and function at the interface of innate and adaptive immunity.


Initiation of a CD8+ T-cell response against an antigen that is not present within antigen-presenting cells. The antigen must be taken up by antigen-presenting cells and then re-routed to the major histocompatibility class I presentation pathway.


The ability of an antigen or vaccine to stimulate an immune response.


A family of chemotactic proteins that are divided into C, CC, CXC and CX3C chemokines, depending on the number and spacing of conserved cysteine residues in the amino-terminal part of the protein. Chemokines are involved in inflammatory-cell recruitment and act through G-protein-coupled receptors.


Genetically identical, for example, a fully inbred strain of mouse.


A T-helper-1 immune response is mediated by pro-inflammatory cytokines that are expressed by CD4+ T cells, such as interferon-γ and tumour necrosis factor-β. It promotes cellular immune responses against intracellular infections and malignancy.


A T-helper-2 immune response involves production, by CD4+ T cells, of cytokines such as interleukin-4, which stimulate antibody production. TH2 cytokines promote secretory immune responses of mucosal surfaces to extracellular pathogens and allergic reactions.


Cells that are derived from the same species, but that differ in the expression of major histocompatibility complex alleles and other genetic polymorphisms.


The accumulation of fluid in the intercellular spaces in tissues, reflecting an increase in vascular permeability or pressure.


Inflammatory disease of the small and large intestine, resulting in significant diarrhoea.


Inflammation of the pituitary gland that results in significant disturbances in endocrine function.

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