Differential lysis of melanoma clones by autologous recombinant interleukin 2-activated lymphocytes. Relationship with spontaneous resistance to doxorubicin (Dx).
To investigate whether human melanoma cells intrinsically resistant to autologous LAKs do exist, and whether a relationship between the level of lysis of LAKs and spontaneous drug resistance can be identified at the clonal level, we studied 44 clones obtained from a metastatic melanoma lesion. The antigenic phenotype of clones revealed a marked heterogeneity in the expression of HLA antigens of classes I and II. The clones were subsequently tested for sensitivity to autologous LAK and for spontaneous resistance to Dx. No clone resistant to autologous LAK was found, although a considerable range of lysis was noted with a normal frequency distribution. Growth in agar of the 2 clones in which lysis was least pronounced (6 and 26) was completely inhibited after co-culture with LAKs, indicating a lack of absolute resistance to these effectors. Spontaneous resistance to Dx, evaluated as ID50, revealed instead that the majority of clones had a low ID50. The frequency distribution of clones showed a left-skewed curve. The percentage of specific 51Cr-release and the ID50 for Dx could be correlated in 25 clones by linear regression. Sensitivity to LAK did not correlate with HLA classes I or II or melanoma-associated antigen expression. These results support the contention that increased LAK sensitivity of tumor cells is associated with drug resistance.
Gambacorti-Passerini
C
C
Division of Experimental Oncology D, Istituto Nazionale Tumori, Milan, Italy.
Rivoltini
L
L
Supino
R
R
Mariani
M
M
Parmiani
G
G
D000951:Antigens, Neoplasm / Q000032:analysis; D002999:Clone Cells; D004317:Doxorubicin / Q000494:pharmacology*; D004351:Drug Resistance; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008545:Melanoma / Q000276:immunology* / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology
D000951:Antigens, Neoplasm; D007376:Interleukin-2; D011994:Recombinant Proteins; D004317:Doxorubicin