Importance of Tumor-specific Cytotoxic CD8+ T-Cells in Eradication of a Large Subcutaneous MOPC-315 Tumor following Low-Dose MclpliaIan Therapy1

We have previously demonstrated that depletion of CDS* T-cells by the use of a monoclonal anti-Lyt-2.2 antibody abolishes the curative effectiveness of low-dose melphalan (i.-phenylalanine mustard; L-PAM) therapy for BALB/c mice bearing a large (>20 mm) s.c. MOPC-315 tumor and extensive métastases (Mokyr et al.. Cancer Res., 49: 45974606, 1989). Here we show that as a consequence of low-dose L-PAM therapy, CDS* T-cells accumulate in the s.c. tumor nodules of MOPC315 tumor bearers. Specifically, an 80-fold increase in the number of CDS* T-cells was seen within 5 days after the chemotherapy. Treatment of MOPC-315 tumor bearers with low-dose L-PAM in conjunction with monoclonal anti-Thy-1.2 or anti-Lyt-2.2 antibody, in contrast to treat ment with monoclonal anti-L3T4 antibody, prevented the appearance of the massive CD8* T-cell infiltrate in the s.c. tumor nodules. Fresh CDS* T-cells derived from s.c. MOPC-315 tumor nodules that were regressing as a consequence of low-dose L-PAM therapy exhibited a potent direct lytic activity against the MOPC-315 plasntacytoma in a short-term in vitro assay. The specificity of the lytic activity exhibited by the CDS* Tcells was illustrated not only by the inability of the CDS* T-cells to lyse two antigenically unrelated thymomas (the WEHI 22.1 and the K.I.-4) and a natural killer-sensitive lymphoma (the YAC-1), but also by their relatively weak lytic activity against an antigenically related plasmacytoma (the MOPC-104E). Thus, CDS* T-cells that infÃ-ltrate the s.c. tumor nodules of MOPC-315 tumor bearers following low-dose L-PAM therapy most likely exploit a CTL-type lytic mechanism to eradicate at least part of the large tumor burden not eliminated by the direct antitumor effects of the drug.