SPONTANEOUS REGRESSION OF HUMAN-MELANOMA NONMELANOMA SKIN-CANCER - ASSOCIATION WITH INFILTRATING CD4(-CELLS() T)

Spontaneous regression occurs in some human malignant melanomas and ba sal cell carcinomas (BCCs). We have compared the cellular infiltrate i n regressing and nonregressing tumors in order to analyze the mechanis m by which regression occurs. Regressing primary melanomas and BCCs we re infiltrated with a larger number of CD4(+), but not CD8(+) T lympho cytes than were seen in nonregressing tumors. The number of interleuki n 2 receptor-positive (early activation marker) but not transferrin re ceptor-positive (intermediate activation marker)T cells was increased, indicating that the infiltrating T cells were activated. Large number s of Langerhans cells, macrophages, and other class II major histocomp atibility complex (MHC)-expressing cells were present but were not inc reased in the regressing tumors. There were no detectable B lymphocyte s, and the regressing tumor cells displayed levels of HLA-DR expressio n similar to those of the nonregressing tumors. Comparison of squamous cell carcinoma (SCCs) with keratoacanthomas (KAs), which are likely t o be a spontaneously regressing form of SCC, also showed increased inf iltration of activated CD4(+), but not CD8(+), T cells within the KA. A murine ultraviolet (UV)-induced squamous tumor that spontaneously re gresses when transplanted into immunocompetent syngeneic mice was also infiltrated with increased numbers of activated CD4(+), but not CD8(), T cells prior to and during rejection. These results indicate that spontaneous regression of human skin tumors is likely to be immunologi cally mediated, and that CD4(+) T lymphocytes seem to mediate this reg ression.