Two distinct mechanisms involved in the infiltration of lymphocytes into tumors.

We have analyzed the mechanism controlling the infiltration of lymphocytes into tumor tissues. W3/25 (+) (helper/inducer phenotype) T cells obtained from tumor tissues of T-9 sensitized rats produced soluble factors. We demonstrated that the soluble factors were responsible for the infiltration of T lymphocytes into tumor tissues by using a modified Boyden chamber technique. We established a system in which we stained filters of the Boyden chamber by an immunoperoxidase technique, thus directly determining the phenotype of cells that had actually migrated into the filters in response to the soluble factors. Upon fractionation of soluble factors produced by W3/25 (+) T cells, four peaks of lymphocyte migration factor (LMF) activity were detected. Peaks B and C exhibited strong LMF activity and specifically attracted R1-10B5 (+) (suppressor/killer phenotype) T cells. Thus, the infiltration of R1-10B5 (+) T cells into tumor tissues was partly explained by LMF produced by tumor-infiltrating W3/25 (+) T cells. The expression of a putative receptor for LMF by lymphocytes may also influence the degree of lymphocyte infiltration into tumors.