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The determinants of tumour immunogenicity

Abstract

Many standard and targeted therapies, as well as radiotherapy, have been shown to induce an anti-tumour immune response, and immunotherapies rely on modulating the host immune system to induce an anti-tumour immune response. However, the immune response to such therapies is often reliant on the immunogenicity of a tumour. Tumour immunogenicity varies greatly between cancers of the same type in different individuals and between different types of cancer. So, what do we know about tumour immunogenicity and how might we therapeutically improve tumour immunogenicity? We asked four leading cancer immunologists around the world for their opinions on this important issue.

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Acknowledgements

L.M.J. wishes to thank The Skip Viragh Pancreatic Cancer Center.

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Correspondence to Thomas Blankenstein, Pierre G. Coulie, Eli Gilboa or Elizabeth M. Jaffee.

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Related links

Glossary

Adaptive immune responses

Responses mediated by antigen-specific lymphocytes and antibodies, they are highly antigen-specific and include the development of immunological memory.

Allogeneic

From different individuals of the same species.

Anergic

A state in which T cells are unresponsive and cannot be activated by antigen.

Antigenicity

The ability to be recognized by the immune system by binding to T and B cell receptors, although this might not result in overt responses.

Autochthonous

Formed from endogenous tissue in the correct anatomical location.

Cancer-germline genes

Embryonic genes that are normally only expressed in male germline cells that become expressed in cancer. Can also be described as cancer-testis genes.

Desmoplasia

The growth of fibrous or connective tissue.

DNA mismatch repair

DNA repair mechanism that corrects mispaired nucleotides that originate during DNA replication and recombination.

Graft-versus-host disease

Inflammatory and tissue-destructive immune reactions that result from the attack on host tissues by infused allogeneic lymphocytes.

Graft-versus-leukaemia

Following allogeneic transplantation of bone marrow or blood stem cells, donor T cells may recognize peptides on leukaemia cells that result in beneficial immune attack.

Human leukocyte antigen

Cell-surface molecules that are encoded by the major histocompatibility complex. These molecules present antigenic peptides to T cells. HLA class I molecules present antigen to CD8+ T lymphocytes, and HLA class II molecules present antigen to CD4+ T lymphocytes.

Immunoediting

Describes the complex relationship between a developing tumour that is under constant pressure from the host immune system. Cancer immunoediting consists of three phases: elimination (that is, cancer immunosurveillance), equilibrium and escape.

Lymphopenia

Reduced numbers of lymphocytes, commonly following radiotherapy or chemotherapy.

Minor histocompatibility

Polymorphic peptides derived from normal cellular proteins that can be recognized in the context of major histocompatibility complex molecules. Immune responses against these polymorphic antigens can result in graft-versus-host reactions, graft rejection or beneficial anti-tumour responses.

Regulatory T (TReg) cells

A T cell subpopulation that suppresses the activation of other T cells and that maintains immune system homeostasis and peripheral tolerance to self-antigens.

Syngeneic

Genetically identical.

Tolerance

The process that ensures that repertoires of B cells and T cells are biased against self-reactivity, which reduces the likelihood of autoimmunity.

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Blankenstein, T., Coulie, P., Gilboa, E. et al. The determinants of tumour immunogenicity. Nat Rev Cancer 12, 307–313 (2012). https://doi.org/10.1038/nrc3246

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