Enhanced growth of murine melanoma in ultraviolet-irradiated skin is associated with local inhibition of immune effector mechanisms.
We have developed a model for studying the role of local immunologic mechanisms in tumor development, in which injection of K1735 melanoma cells into the UV-irradiated ears of C3H mice results in a significantly higher incidence of tumors than injection into unirradiated ears. This effect of UV irradiation is immunologically mediated. We hypothesized that UV blocks the efferent arm of the immune response, thereby facilitating tumor development within the irradiated site. We demonstrate that elicitation of a delayed type hypersensitivity response to alloantigen is diminished in UV-irradiated ears. in addition, tumor rejection is impaired in melanoma-immune mice challenged in UV-irradiated ears, even though such mice exhibit systemic immunity when challenged in a nonirradiated site. The ability of immune lymphoid cells to inhibit melanoma growth when mixed with tumor cells and injected into the ears was inhibited by prior UV irradiation of the ears, indicating that the activity of immune effector cells is abrogated in the UV-irradiated microenvironment. Analysis of lymphoid cells in growing tumors indicated that the number of CD8+ T lymphocytes was reduced in the UV-irradiated site. We conclude that efferent immune responses are impaired in UV-irradiated tissue and suggest that the impairment may involve reductions in both the number and the activity of immune effector cells. These studies illustrate that conditions in the local microenvironment during the early stages of tumor growth may profoundly influence the outcome of the host-tumor interaction.
Donawho
C K
CK
Department of Immunology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Muller
H K
HK
Bucana
C D
CD
Kripke
M L
ML
D000818:Animals; D002455:Cell Division / Q000276:immunology / Q000528:radiation effects; D002465:Cell Movement / Q000528:radiation effects; D005260:Female; D006084:Graft Rejection / Q000209:etiology / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular / Q000528:radiation effects; D007519:Isoantigens / Q000276:immunology; D008545:Melanoma / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008809:Mice, Inbred C3H; D009381:Neoplasms, Radiation-Induced / Q000276:immunology* / Q000473:pathology*; D012867:Skin / Q000276:immunology / Q000528:radiation effects; D012878:Skin Neoplasms / Q000209:etiology / Q000276:immunology* / Q000473:pathology*; D014466:Ultraviolet Rays / Q000009:adverse effects*
D007519:Isoantigens