Page 1161 - Veterinary Immunology, 10th Edition

leukemic T cells and NK cells, colon adenocarcinoma cells,
VetBooks.ir melanomas, and hepatocellular carcinomas. Since cytotoxic T cells

may also express CD95, cytotoxicity may work in reverse and
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CD95L tumor cells may kill the T cells. At the same time, these
cancer cells may downregulate their own CD95 so that they become
resistant to cell-mediated cytotoxicity. Some cancer cells such as
those in lung carcinomas may secrete decoy receptors for CD95L.
These decoy receptors bind CD95L and prevent it from binding to

CD95. Cancer cells that downregulate CD95 while producing decoy
receptors may be resistant to T cell cytotoxicity.

Regulatory Cells

Much of the immunosuppression in tumor-bearing individuals may

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be due to regulatory cells. These may be CD8 Treg cells, IL-10–
secreting Th2 cells, M2 macrophages, or even B cells. Enhanced
regulatory cell activity can be detected in many tumor-bearing
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animals. Thus in normal dogs, FoxP3 Treg cells constitute about 5%
of blood T cells and 10% of lymph node T cells. In tumor-bearing
dogs, however, they may constitute as many as 7.5% in blood and
17% in tumor-draining lymph nodes. Dogs with osteosarcomas
have elevated Treg and fewer CD8 cells in blood, lymph nodes, and

tumors. The CD8/Treg ratio is significantly lower in tumor-bearing
dogs, and dogs with the greatest decrease have a shorter survival
time. Treg numbers also rise in dogs with carcinomas.

Myeloid-Derived Suppressor Cells

Myeloid-derived suppressor cells (MDSCs) are immature myeloid
cells that normally develop into macrophages, granulocytes, and
dendritic cells. They are generated by soluble factors produced by

cancer cells and are attracted by chemokines or hypoxia to the
tumors. Once inside tumors, MDSCs suppress cytotoxic T cell
responses by expressing the inhibitory surface marker PD-L1, and
by secreting immunosuppressive mediators such as arginase, IL-10,

TGF-β, reactive oxygen species, nitric oxide, and peroxynitrite.
Peroxynitrite causes nitrate addition to TCRs and thus inactivates
them. MDSCs also produce arginase that impairs T cell function by

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