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Mutations and regulatory anomalies effecting tumor cell immune functions

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Abstract

The immune system is capable of interacting with tumor cells in such a way as to lead to tumor cell death, and this knowledge has inspired therapies to manipulate patient immune systems to eradicate cancer. However, tumor cells are able to mitigate the antitumor immune response, a fact that has rarely been addressed in the design of immunotherapies. There are many different tumor cell immune functions that play a role in mitigating the antitumor immune response. In some cases, these functions appear to be intimately associated with the tumor cell abnormalities that lead to loss of growth control, such as the cases where classical tumor suppressor proteins regulate tumor cell immune function genes. In other cases, tumor cell mutations appear to affect only the antitumor response, such as tumor cell mutations that eliminate MHC class I expression. Here I review the bases for tumor cell immune functions, noting in particular where tumor cell mutations, the gold standard for identifying a tumor-specific function, are known to be responsible for the tumor cell immune function. This review also discusses other known regulatory anomalies, in the absence of a known mutation, that are apparently important for tumor development and that regulate tumor cell immune functions. Surprisingly, in many cases where the tumor cell immune function is well understood in terms of its effect on the antitumor immune response, the tumor abnormality underlying the tumor cell immune function is completely uncharacterized.

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Abbreviations

NK:

natural killer (cell)

MHC:

major histocompatibility complex

SPIF:

specialized immune function (cell)

KIR:

killer cell inhibitory receptor

STAT:

SIGNAL transducer and activator of transcription

IFN:

interferon

TAP:

transporter for antigen processing

LOH:

loss of heterozygosity

CIITA:

class II transactivator

HDAC:

histone deacetylase

IRF-1:

interferon regulatory factor-1

IL-8:

interleukin 8

TGF-β:

transforming growth factor β

VEGF:

vascular endothelial cell growth factor

ICAM:

intracellular adhesion molecule

MMP:

matrix metalloprotease

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Acknowledgements

The author thanks members of the Moffitt Cancer Immunology Program for critical reading of the manuscript. The author's work described above was supported by grants from the National Institutes of Health and the American Cancer Society.

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  1. Department of Biochemistry and Molecular Biology, College of Medicine, Immunology Program, Moffitt Cancer Center, University of South Florida, Tampa, FL 33612, USA

    George Blanck

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Blanck, G. Mutations and regulatory anomalies effecting tumor cell immune functions. Cancer Immunol Immunother 53, 1–16 (2004). https://doi.org/10.1007/s00262-003-0418-3

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