Page 1156 - Veterinary Immunology, 10th Edition

VetBooks.ir Box 35.1

The Role of the Microbiota in Cancer

Surveillance

When cancer patients are treated with modern immunotherapy,
some respond much more effectively than others. One reason for
these differences is ascribed to their microbiota. Anticancer
immune T cells are shaped by the microbiota. This may be due to

cross-reactivity between microbial and tumor antigens, or
microbial products stimulating PRRs that then influence the type
and intensity of immune responses. Thus the effectiveness of anti–

CTLA-4 therapy in mice depends upon the presence of Bacteroides
fragilis in their intestine. Anti–PD-1 therapy was more effective in
the presence of Bifidobacterium. Some investigators have developed
a “cancer hygiene hypothesis” suggesting that recent increases in
the prevalence of some cancers may be due to dysbiosis or

underexposure to certain bacterial species.

Zitvogel L, Ayyoub M, Routy B, Kroemer G: Microbiome and anti-cancer
immunosurveillance, Cell 165:276-287, 2016.

Macrophage-Mediated Immunity

Solid tumors may be infiltrated by macrophages attracted to the
tumor by proinflammatory cytokines and prostaglandins. One of

their roles is to promote and regulate angiogenesis. Their presence
and activities may determine progression to malignancy.
Macrophages may promote cancer cell proliferation and metastasis

by releasing growth factors such as TGF-β, PDGF, and FGF. Cancer
cells expressing the receptor for colony-stimulating factor-1 (CSF-1)
tend to be more aggressive and metastasize more than those that
lack this receptor. M1 macrophages may have antitumor activities,
and secrete cytotoxic molecules, including potent oxidants.

Nonspecific activation of macrophages by bacillus Calmette-Guérin
(BCG) or Propionibacterium acnes results in enhanced production of
IL-1 or TNF-α and subsequent enhancement of helper T cell and
NK cell activity. IL-1 has a cytostatic effect on some tumors, and

TNF-α may have potent antitumor activity. Unfortunately,
malignant tumors inhibit macrophage activation, and tumor-

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