Lymphokine-activated killer (LAK) and monocyte-mediated cytotoxicity on tumor cell lines resistant to antitumor agents.
In this study we have examined the susceptibility of tumor cell lines exhibiting different patterns of resistance to chemotherapeutic agents, to the cytotoxic action of lymphokine-activated killer (LAK) cells and activated monocytes. The susceptibility of tumor cells with pleiotropic drug resistance to these cytotoxic mechanisms was not different from that of their parental, chemo-sensitive cell lines. Tumor lines used in this study included three human cell lines (LOVO N and LOVO/Dx, I-407 and I-407/Dx, MCF7 and MCF7a) selected for being resistant to doxorubicin and showing a pleiotropic pattern of resistance, and the murine ovarian reticulum cell sarcoma M5076 and its variants resistant to individual antitumor agents (cisplatin, cyclophosphamide and 5-aza-2'-deoxycytidine). These results demonstrate that drug-resistant tumor cell lines, irrespective of the pattern of resistance, were susceptible to the in vitro cytotoxicity mediated by LAK cells and activated monocytes with levels of lysis similar to those of parental chemosensitive lines. Moreover, freshly isolated tumor cells from ovarian cancer patients unresponsive to different chemotherapeutic treatments (operationally drug-resistant) were significantly killed in vitro by LAK cells. These findings support the concept that activated effector cells have the potential to complement conventional chemotherapy by eliminating drug-resistant tumor variants.
Allavena
P
P
Laboratory of Immunology, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Damia
G
G
Colombo
T
T
Maggioni
D
D
D'Incalci
M
M
Mantovani
A
A
D000818:Animals; D001943:Breast Neoplasms / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007167:Immunotherapy; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D009000:Monocytes / Q000276:immunology*; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000628:therapy; D012513:Sarcoma, Experimental / Q000276:immunology* / Q000628:therapy; D014407:Tumor Cells, Cultured
D007376:Interleukin-2