CD11c-POSITIVE CELLS INFILTRATING MELANOMA
Primary cutaneous melanoma (PCM) is commonly associated with a dermal infiltrate, possibly suggesting a defense mechanism of the host towards abnormal melanocytes. In fact, such a dermal infiItrate, mainly comprised of Langerhans cells (LC), macrophages and T cells, may presumably cause, according to some suggestions, even the regression of PMC. However, the exact mechanism of defense yielded by the dermal infiltrate against the abnormal melanocytes is up to date not completely clear.
Recently, a heterodimeric protein, composed of an alpha subunit of 150kD noncovalently associated to a beta subunit of 95kD, named gp150,95 (CD11c/CD18), was detected on the membrane of monocytes, macrophages, NK cells (reviewed by 1), a minor part of cytotoxic T lymphocytes (CTL) (2), and on LC (3,4). Such gp 150,95 molecule is involved in cell-mediated cytolysis by CTL (2). Further, it was shown to be able to uniquely trigger the adhesion of mononuclear cells expressing it to monolayers of melanoma cells (5). In fact, antibodies directed to the alpha chain of gp150,95 (anti-CD11c antibodies ) inhibited adhesion thus, the monocyte adhesion to melanoma monolayers is caused by the CD11c moiety (5).
We intended therefore to investigate the expression of the CD11c molecule on the cells infiltrating the PCM, using a series of "in situ" immunostaining procedures, both in light microscopy and in immunoelectron microscopy, developped in our laboratory (6,7,8,9), on "early invasive" melanomas. Our results showed a consistent proportion of dermal CD11c-positive cells, including macrophages, LC and lymphocytes, infiltrating the "early invasive" PCM.
The presence of macrophages and especially LC in the dermal infiltrate of PCM has been associated with the hypothesis that such antigen-presenting cells, pulsed by melanoma antigens, could be essential for initiation and maintenance of a cutaneous immune response against early transformed melanocytes (10,11). This hypothesis seems to be extended by the results of the present study. We indeed observed that a vast proportion of mononuclear cells infiltrating PCM was CD11c-positive, including LC, macrophages and lymphocytes. Such CD11c expressions might suggest at least three different hypothetical roles for the CD11c-positive mononuclear cells infiltrating PCM.
(1) The CD11c adhesive moiety could subserve, at least partly, the contact of both LC
and macrophages with abnormal melanocytes, as demonstrated "in vitro" (5),
possibly to capture and then "process" the melanocytic neoantigens.
(2) Subsequently, the presence on the membrane of antigen-presenting cells of adhesive proteins could facilitate the interaction with T lymphocytes for clustering
(12), thought to be necessary for an efficient antigen-presentation.
(3) It seems conceivable that, in a further phase, the CD11-positive lymphocytes, and perhaps also the CD11c-positive macrophages, could play a cytolytic role against melanoma cells, acting, as demonstrated "in vitro" for human CTL clones (2), at the level of conjugate formation between effector and target cells.
In conclusion, our findings demonstrate the occurence of a quantity of CD11c-positive
cells infiltrating the "early invasive " PCM , possibly involved in (1)
neoantigen recruitment , (2) neoantigen presentation and even (3) cytolytic activity
against tranformed melanocytes, thus playing a key role in the host resistance, and
possibly favouring the regression of PCM.
1 . Springer TA et al : J Immunol 136, 240, 1986
2 . Keizer GD et al : J Immunol 138, 3130, 1987
3 . De Panfilis G et al : In "Langerhans cell", J Libbey Eurotext, London 1988
4 . De Panfilis G et al : J Invest Dermatol, in press
5 . Te Velde AA et al : Immunology 61, 261, 1987
6 De Panfilis G et al : Acta Dermatovenereol (Stockholm) 59, 219, 1979
7 . De Panfilis G : Arch Dermatol Res 275, 407, 1983
8 . De Panfilis G et al : J Invest Dermatol 87, 510, 1986
9 . De Panfilis G et al : Br J Dermatol 115, 351, 1987
10. Nestor MS and Cochran AJ : Pigment Cell Res 1, 22, 1987
11. Stene MA et al : J Invest Dermatol 91, 125, 1988
Giuseppe DE PANFILIS
Clinica Dermatologica Universita