Tumor infiltration by adoptively transferred T cells is independent of immunologic specificity but requires down-regulation of L-selectin expression

Adoptive immunotherapy,vith anti-CD3/IL-2 activated tumor-draining lymph no de (LN) T cells is capable of eradicating tumor established at various hist ological sites. Tumor-specific effector lymphocytes have recently been iden tified to be LN T cells with down-regulated L-selectin (L-selectin(-)). Usi ng fluorochrome labeling, the present study determined the early traffickin g pattern of systemically transferred cells. In mice with 10-day establishe d pulmonary 3-methylcholanthrene (MCA) 205 metastases, accumulation of cell s in tumors was evident as early as 2 h after i,v, cell transfer, and, by 2 4 h, > 50-fold higher numbers of cells were seen in metastases than in norm al tissues. Similarly, transferred cells selectively infiltrated s,c, tumor s, albeit at a lower rate. Analysis of the transferred cells isolated from recipient mice revealed that tumor-infiltrating cells were mostly L-selecti n(>95%), By contrast, only 24% and 58% L-selectin- cells were found in the LN and spleen, respectively. The ability of L-selectin(-) cells to accumula te at tumor sites was confirmed by the transfer of purified cell population s. Despite this selective tumor infiltration, the trafficking pattern did n ot reflect antigenetic specificity, and tumor regression occurred only afte r the transfer;of tumor-specific effector cells. These results, thus, sugge st that there are two distinct mechanisms operative in successful adoptive immunotherapy, Early infiltration of tumors by transferred cells is dictate d by the physiological properties of cells and is independent on their immu nologic specificity. Tumor regression, however, requires immunologically sp ecific interactions at the site of tumor.