Urocanic acid (UCA) accumulates in the epidermis after deamination of
histidine. UCA isomerizes from the trans to the cis form upon exposure
to environmental UV radiation. Cis-UCA is immunosuppressive in severa
l models. Topically applied cis-UCA was reported to enhance the cutane
ous tumor yield in chronically UV-irradiated mice, suggesting involvem
ent of cis-UCA in photocarcinogenesis. Since Langerhans cells (LC) are
capable of presenting tumor-associated Ags (TAA) for primary and seco
ndary tumor-immune responses, we examined the effects of trans- and ci
s-UCA on LC tumor Ag presentation in a model of immunity to the S1509a
spindle cell tumor (H-2(a)). In this system, induction of immunity re
quires exposure of LC to granulocyte-macrophage CSF. Naive CAF, (H-2(a
/d)) mice were immunized against S1509a by injection with granulocyte-
macrophage CSF-exposed and TAA-pulsed epidermal cells (EC), as assesse
d by growth inhibition of inoculated tumor cells, Incubation of EC in
cis-, but not trans-UCA completely inhibited Ag presentation in this s
ystem. Neither histamine antagonists nor indomethacin reversed these e
ffects of cis-UCA. The ability of trans- and cis-UCA to modulate EC pr
esentation of TAA for secondary immune responses was also examined. EC
were pulsed with TAA in vitro and then injected into hind footpads of
tumor-immune mice, After 24 h, footpad swelling was assessed as a mea
sure of delayed-type hypersensitivity. Incubation with cis-, but again
not trans-UCA before TAA exposure significantly inhibited elicitation
of delayed-type hypersensitivity. These data indicate that cis-UCA ma
y be an important regulator of LC Ag-presenting function in tumor-immu
ne responses, and thus may play a role in photocarcinogenesis.