PT  - JOURNAL ARTICLE
AU  - Barker, Edward
AU  - Wise, James A.
AU  - Dray, Sheldon
AU  - Mokyr, Margalit B.
TI  - Lysis of Antigenically Unrelated Tumor Cells Mediated by Lyt 2<sup>+</sup> Splenic T-Cells from Melphalan-cured MOPC-315 Tumor Bearers
DP  - 1989 Sep 15
TA  - Cancer Research
PG  - 5007--5015
VI  - 49
IP  - 18
4099  - http://cancerres.aacrjournals.org/content/49/18/5007.short
4100  - http://cancerres.aacrjournals.org/content/49/18/5007.full
SO  - Cancer Res1989 Sep 15; 49
AB  - We have previously shown that mice cured of a large MOPC-315 tumor following low-dose melphalan (l-phenylalanine mustard, L-PAM) therapy can exert, upon challenge with MOPC-315 tumor cells, an antitumor effect against innocent bystander tumor cells present within the same tumor site (Barker, E., and Mokyr, M. B. Cancer Immunol. Immunother., 25: 215–224, 1987). Here we show that T-cells are important for the MOPC-315-induced rejection of MOPC-104E tumor cells present within the same site. To further characterize the innocent bystander killing activity exerted by L-PAM-cured MOPC-315 tumor bearers upon stimulation with MOPC-315 tumor cells, we established the in vitro conditions under which lymphoid cells from L-PAM-cured MOPC-315 tumor bearers can exert an antitumor effect against innocent bystanders. Specifically, we established that spleen cells from mice that just completed the rejection of a large MOPC-315 tumor following low-dose L-PAM therapy can, upon stimulation with MOPC-315 tumor cells, bring about the killing of antigenically unrelated tumor cells in a 12-h 51Cr release assay. The magnitude of lysis of EL4 and WEHI 22.1 tumor cells by MOPC-315 in vitro-immunized (IVI) spleen cells from L-PAM-cured MOPC-315 tumor bearers can be substantially enhanced upon reexposure of the spleen cells to MOPC-315-associated antigens during the 12-h 51Cr release assay. The lysis of innocent bystander tumor cells by these MOPC-315-IVI spleen cells was found to be mediated by T-cells of the Lyt 2 and not the L3T4 phenotype. These Lyt 2+ T-cells did not appear to mediate their lytic activity for innocent bystander tumor cells via effector macrophages, since a drastic reduction in macrophage frequency among the MOPC-315-IVI spleen cells just prior to assessing the lytic activity of the spleen cells did not reduce, but actually enhanced, the magnitude of EL4 lysis. In addition, a Lyt 2+ T-cell clone derived from mice cured of a large MOPC-315 tumor by a low dose of drug was capable, upon stimulation with MOPC-315 tumor cells, of exerting a potent lytic effect against EL4 and WEHI 22.1 tumor cells in the 12-h 51Cr release assay. Thus, Lyt 2+ T-cells independent of effector macrophages are responsible for lysis of innocent bystander tumor cells by MOPC-315-IVI spleen cells from L-PAM-cured MOPC-315 tumor bearers. ©1989 American Association for Cancer Research.