Abstract
Spontaneous regression occurs in some human malignant melanomas and basal cell carcinomas (BCCs). We have compared the cellular infiltrate in regressing and nonregressing tumors in order to analyze the mechanism by which regression occurs. Regressing primary melanomas and BCCs were infiltrated with a larger number of CD4+, but not CD8+, T lymphocytes than were seen in nonregressing tumors. The number of interleukin 2 receptor-positive (early activation marker) but not transferrin receptor-positive (intermediate activation marker) T cells was increased, indicating that the infiltrating T cells were activated. Large numbers of Langerhans cells, macrophages, and other class II major histocompatibility complex (MHC)-expressing cells were present but were not increased in the regressing tumors. There were no detectable B lymphocytes, and the regressing tumor cells displayed levels of HLA-DR expression similar to those of the nonregressing tumors. Comparison of squamous cell carcinoma (SCCs) with keratoacanthomas (KAs), which are likely to be a spontaneously regressing form of SCC, also showed increased infiltration of activated CD4+, but not CD8+, T cells within the KA. A murine ultraviolet (UV)-induced squamous tumor that spontaneously regresses 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 immunologically mediated, and that CD4+ T lymphocytes seem to mediate this regression.
Résumé
Il semble que, chez l'homme, un certain nombre de mélanomes malins et de carcinomes basocellulaires (CBC) soient capables de régression spontanée. Nous avons comparé la cellularité des infiltrats des tumeurs qui régressent par rapport à celles qui ne régressent pas pour essayer de comprendre le mécanisme par lequel la régression se produisait. Les mélanomes et les CBC qui régressent avaient un plus grand nombre de lymphocytes T CD4+ mais pas de lymphocytes T CD8+ par rapport aux tumeurs qui ne régressaient pas. Le nombre de récepteurs IL-2 (early activation marker) de ces mêmes lymphocytes T était plus élevé alors que celui des récepteurs transferrine ne l'était pas, indiquant que les cellules T infiltrantes étaient activées. Il y avait aussi un plus grand nombre de cellules de Langerhans, de macrophages et d'autres cellules d'expression de la classe II MHC dans les tumeurs qui régressaient par rapport aux tumeurs qui ne régressaient pas. Il n'y avait pas de lymphocytes B et les tumeurs qui régressaient présentaient un expression HLA-DR similaire à celle de tumeurs qui ne régressaient pas. En comparant des carcinomes épithéliaux (CE) avec des kératocarcinomes (KC), (probablement une forme de régression spontanée de CE), la cellularité de ces derniers était augmentée en ce qui concerne les lymphocytes activés CD4+ mais pas les lymphocytes CD8+ par rapport aux CE. Une tumeur épithéliale induite par les UV chez la souris qui régressait spontanément lorsque l'on la transplante chez une souris syngénique immunocompétante présentait également une augmentation de lymphocytes CD4+ mais pas de CD8+ avant et pendant le rejet. Ces résultats indiquent que la régression spontanée des tumeurs de la peau humaine est probablement immunomédiée et que le médiateur est probablement le lymphocyte CD4+.
Resumen
La regresión espontánea ocurre en un porcentaje de los melanomas malignos y de los carcinomas basocelulares humanos. Hemos comparado el infiltrado celular en los tumores en regresión y en no regresión con el objeto de analizar el mecanismo por el cual ocurre la regresión. Los melanomas primarios en regresión y los carcinomas basocelulares aparecieron infiltrados por un número mayor de linfocitos T CD4+ pero no CD8+ en comparación con los tumores en no regresión. El número de receptores + de IL-2 (un marcador de activación precoz), pero no de receptores + de transferrina (marcador de activación intermedia) apareció aumentado, indicando que las células T infiltrantes habían sido activadas. Un gran número de células de Langerhans, macrófagos y otras células de la clase II MHC estuvieron presentes, aunque no incrementadas en los tumores en regresión. No hubo linfocitos B detectables, y los tumores en regresión exhibieron niveles similares de expresión HLA-DR que los tumores en no regresión. La comparación del carcinoma escamocelular con queroacantomas, que posiblemente son formas de regresión espontánea de un carcinoma escamocelular, también exhibieron infiltración por células T activadas CD4+ pero no CD8+ dentro del queroacantoma. Un tumor murino escamoso inducido que regresa espontáneamente cuando se lo transplanta a ratones singénicos immunocompetentes también apareció infiltrado con un aumentado número de células T CD4+ pero no CD8+ antes y durante la fase de rechazo. Estos resultados indican que la regresión espontánea de los tumores humanos de la piel posiblemente sea un fenómeno de mediación inmunitaria y que los linfocitos T CD4+ parecen ser los mediadores de la regresión.
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Halliday, G.M., Patel, A., Hunt, M.J. et al. Spontaneous regression of human melanoma/nonmelanoma skin cancer: Association with infiltrating CD4+ T cells. World J. Surg. 19, 352–358 (1995). https://doi.org/10.1007/BF00299157
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DOI: https://doi.org/10.1007/BF00299157