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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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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DOI: https://doi.org/10.1038/nrc3246
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